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Alvarado-Flores F, Chu T, Catalano P, Sadovsky Y, O'Tierney-Ginn P. The expression of chromosome 19 miRNA cluster members during insulin sensitivity changes in pregnancy. Placenta 2025; 161:23-30. [PMID: 39847922 PMCID: PMC11867847 DOI: 10.1016/j.placenta.2025.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 01/10/2025] [Accepted: 01/15/2025] [Indexed: 01/25/2025]
Abstract
HYPOTHESIS Declines in insulin sensitivity during pregnancy important for fetal growth are associated with impairments in skeletal muscle post-receptor insulin signaling. The primary initiator of these changes is unknown but believed to originate in the placenta. We hypothesize that placental miRNAs are associated with maternal sensitivity changes and impact insulin-sensitive mechanisms in target tissues in vitro. METHODS Using qPCR, miRNA expression was measured in plasma in early (12-16 wk) and late (34-36 wk) gestation (N = 39) and placental tissue at term (37-41 weeks) (N = 142) collected from independent cohorts. Insulin-sensitive glucose uptake was measured in human skeletal muscle myoblasts exposed to miRNA mimics in vitro. Multi-linear and binomial regression models were generated to test for associations between miRNAs, insulin sensitivity and fetal growth outcomes, adjusting for relevant clinical variables. P < 0.05 was considered significant. RESULTS Placental expression of chromosome 19 miRNA cluster (C19MC) members was higher in patients with obesity and positively correlated with maternal HOMA-IR (Homeostatic Model Assessment for Insulin Resistance; miR-516b-5p, miR-517a-3p, miR-1283). Placental expression of miR-517a-3p was higher in offspring with high adiposity and birthweight. Plasma miR-517a-3p in early and late pregnancy was related to decreases in insulin sensitivity during pregnancy. Mimics for miR-517a-3p and miR-524-3p both impaired insulin-sensitive glucose uptake in human skeletal myocytes in vitro. DISCUSSION Our findings based on data from two independent pregnancy cohorts and in vitro studies support a role for members of the C19 cluster of miRNAs - particularly miR-517a-3p - in physiological changes in insulin sensitivity over pregnancy, which may impact fetal growth.
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Affiliation(s)
| | - Tianjiao Chu
- Magee Women's Research Institute, University of Pittsburgh, Pittsburgh, PA, USA
| | - Patrick Catalano
- Mother Infant Research Institute, Tufts Medicine, Boston, MA, USA; Dept Obstetrics & Gynecology, Tufts University, Boston, MA, USA
| | - Yoel Sadovsky
- Magee Women's Research Institute, University of Pittsburgh, Pittsburgh, PA, USA
| | - Perrie O'Tierney-Ginn
- Mother Infant Research Institute, Tufts Medicine, Boston, MA, USA; Dept Obstetrics & Gynecology, Tufts University, Boston, MA, USA.
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Cho Y, Choi EY, Choi A, Han JY, Ye BD, Kim JH, Shin JY. Anti-Tumor Necrosis Factor Therapy and the Risk of Gestational Diabetes in Pregnant Women With Inflammatory Bowel Disease. Am J Gastroenterol 2025; 120:241-250. [PMID: 39315687 DOI: 10.14309/ajg.0000000000003100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 09/18/2024] [Indexed: 09/25/2024]
Abstract
INTRODUCTION Anti-tumor necrosis factor (anti-TNF) therapy may improve insulin sensitivity, and its impact during pregnancy remains unclear. We aimed to assess the risk of gestational diabetes mellitus (GDM) associated with anti-TNF treatment among pregnant women with inflammatory bowel disease (IBD). METHODS This nationwide cohort study included patients with IBD in Korea from 2010 to 2021. Anti-TNF exposure was identified from the last menstrual period (LMP) to LMP + 140 days. The development of GDM was assessed from LMP + 141 days to delivery. We performed overlap weighting to balance the covariates and used a generalized linear mixed model to measure the risk ratio (RR) and 95% confidence intervals (CIs). The anti-TNF group was compared with the unexposed group, as well as with the immunosuppressant, 5-aminosalicylate, and untreated groups. RESULTS A total of 3,695 pregnancies in women with IBD were identified, of which 338 (9.2%) were exposed to anti-TNFs. GDM was found in 7.1% of the pregnancies exposed to anti-TNFs as compared with 11.0% of those unexposed. The crude and weighted RRs for GDM risk were 0.64 (95% CI 0.43-0.96) and 0.68 (95% CI 0.55-0.84), respectively. The weighted RR when compared with the immunosuppressant, 5-aminosalicylate, and untreated groups was 0.70 (95% CI 0.41-1.18), 0.71 (95% CI 0.52-0.95), and 0.85 (95% CI 0.59-1.24), respectively. DISCUSSION This nationwide cohort reported a decreased risk of GDM among patients who used anti-TNFs during early pregnancy compared with those unexposed. GDM risk may become a consideration in the decision-making process when choosing treatment options for pregnant women with a risk factor for GDM.
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Affiliation(s)
- Yongtai Cho
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
| | - Eun-Young Choi
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
| | - Ahhyung Choi
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
- Harvard-MIT Center for Regulatory Science, Harvard Medical School, Boston, Massachusetts, USA
| | - Jung Yeol Han
- Korea Mothersafe Counseling Center, Department of Obstetrics and Gynecology, Inje University Ilsan Paik Hospital, Goyang, South Korea
| | - Byong Duk Ye
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Ju Hwan Kim
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
- Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea
| | - Ju-Young Shin
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
- Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea
- Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, South Korea
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Patra S, McMillan CJ, Snead ER, Warren AL, Cosford K, Chelikani PK. Feline Diabetes Is Associated with Deficits in Markers of Insulin Signaling in Peripheral Tissues. Int J Mol Sci 2024; 25:13195. [PMID: 39684905 DOI: 10.3390/ijms252313195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 12/03/2024] [Accepted: 12/06/2024] [Indexed: 12/18/2024] Open
Abstract
Like humans, cats have a strong relationship between decreasing insulin sensitivity and the development of diabetes with obesity. However, the underlying molecular mechanisms of impaired insulin secretion and signaling in cats remain largely unknown. A total of 54 client-owned nondiabetic lean (n = 15), overweight (n = 15), and diabetic (n = 24) cats were included in the study. The pancreas, liver, and skeletal muscle were quantified for mRNA and protein abundances of insulin and incretin signaling markers. Diabetic cats showed increased liver and muscle adiposity. The pancreas of diabetic cats had decreased transcript abundances of insulin, insulin receptor, insulin-receptor substrate (IRS)-1, glucose transporters (GLUT), and protein abundance of mitogen-activated protein kinase. In treated diabetics, protein abundance of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide receptors, total and phosphorylated Akt, and GLUT-1 were increased in the pancreas, whereas untreated diabetics had downregulation of markers of insulin and incretin signaling. In the muscle and liver, diabetic cats had reduced mRNA abundances of insulin receptor, IRS-1/2, and phosphatidylinositol-3-kinase, and reduced protein abundances of GLUT-4 and phosphatidylinositol-3-kinase-p85α in muscle. We demonstrate that feline diabetes is associated with ectopic lipid deposition in the liver and skeletal muscle, deficits in insulin synthesis and incretin signaling in the pancreas, and impaired insulin signaling in the muscle and liver. These findings have implications for understanding the pathophysiological mechanisms of obesity and diabetes in humans and pets.
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Affiliation(s)
- Souvik Patra
- School of Veterinary Medicine, Texas Tech University, 7671 Evans Drive, Amarillo, TX 79106, USA
| | - Chantal J McMillan
- Faculty of Veterinary Medicine, University of Calgary, 3280 Hospital Dr. NW, Calgary, AB T2N 4Z6, Canada
| | - Elisabeth R Snead
- Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada
| | - Amy L Warren
- Faculty of Veterinary Medicine, University of Calgary, 3280 Hospital Dr. NW, Calgary, AB T2N 4Z6, Canada
| | - Kevin Cosford
- Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada
| | - Prasanth K Chelikani
- School of Veterinary Medicine, Texas Tech University, 7671 Evans Drive, Amarillo, TX 79106, USA
- Faculty of Veterinary Medicine, University of Calgary, 3280 Hospital Dr. NW, Calgary, AB T2N 4Z6, Canada
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Mora-Ortiz M, Rivas-García L. Gestational Diabetes Mellitus: Unveiling Maternal Health Dynamics from Pregnancy Through Postpartum Perspectives. OPEN RESEARCH EUROPE 2024; 4:164. [PMID: 39355538 PMCID: PMC11443192 DOI: 10.12688/openreseurope.18026.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Accepted: 10/29/2024] [Indexed: 10/03/2024]
Abstract
Gestational Diabetes Mellitus (GDM) is the most frequent pregnancy-related medical issue and presents significant risks to both maternal and foetal health, requiring monitoring and management during pregnancy. The prevalence of GDM has surged globally in recent years, mirroring the rise in diabetes and obesity rates. Estimated to affect from 5% to 25% of pregnancies, GDM impacts approximately 21 million live births annually, according to the International Diabetes Federation (IDF). However, consensus on diagnostic approaches remains elusive, with varying recommendations from international organizations, which makes the comparison between research complicated. Compounding concerns are the short-term and long-term complications stemming from GDM for mothers and offspring. Maternal outcomes include heightened cardiovascular risks and a notable 70% risk of developing Type 2 Diabetes Mellitus (T2DM) within a decade postpartum. Despite this, research into the metabolic profiles associated with a previous GDM predisposing women to T2D remains limited. While genetic biomarkers have been identified, indicating the multifaceted nature of GDM involving hormonal changes, insulin resistance, and impaired insulin secretion, there remains a dearth of exploration into the enduring health implications for both mothers and their children. Furthermore, offspring born to mothers with GDM have been shown to face an increased risk of obesity and metabolic syndrome during childhood and adolescence, with studies indicating a heightened risk ranging from 20% to 50%. This comprehensive review aims to critically assess the current landscape of Gestational Diabetes Mellitus (GDM) research, focusing on its prevalence, diagnostic challenges, and health impacts on mothers and offspring. By examining state-of-the-art knowledge and identifying key knowledge gaps in the scientific literature, this review aims to highlight the multifaceted factors that have hindered a deeper understanding of GDM and its long-term consequences. Ultimately, this scholarly exploration seeks to promote further investigation into this critical area, improving health outcomes for mothers and their children.
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Affiliation(s)
- Marina Mora-Ortiz
- Lipids and Atherosclerosis Unit, Internal Medicine, Reina Sofia University Hospital, Córdoba, Andalucía, 14004, Spain
- GC09-Nutrigenomics and Metabolic Syndrome, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Andalucía, 14004, Spain
- Department of Medical and Surgical Sciences, Universidad de Cordoba, Córdoba, Andalucía, 14004, Spain
| | - Lorenzo Rivas-García
- Department of Physiology, Institute of Nutrition and Food Technology “José Mataix Verdú”, Biomedical Research Centre, Universidad de Granada, Armilla, Granada, Andalucia, 18016, Spain
- Sport and Health Research Centre, Universidad de Granada, Armilla, Granada, Andalucia, 18016, Spain
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Dada A, Habibi J, Naz H, Chen D, Lastra G, Bostick BP, Whaley-Connell A, Hill MA, Sowers JR, Jia G. Enhanced ECCD36 signaling promotes skeletal muscle insulin resistance in female mice. Am J Physiol Endocrinol Metab 2024; 327:E533-E543. [PMID: 39196801 PMCID: PMC11482271 DOI: 10.1152/ajpendo.00246.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 08/19/2024] [Accepted: 08/24/2024] [Indexed: 08/30/2024]
Abstract
Consumption of a Western diet (WD) increases CD36 expression in vascular, hepatic, and skeletal muscle tissues promoting lipid metabolic disorders and insulin resistance. We further examined the role of endothelial cell-specific CD36 (ECCD36) signaling in contributing to skeletal muscle lipid metabolic disorders, insulin resistance, and their underlying molecular mechanisms. Female ECCD36 wild-type (ECCD36+/+) and knock-out (ECCD36-/-) mice, aged 6 wk, were provided with either a WD or a standard chow diet for a duration of 16 wk. ECCD36+/+ WD mice were characterized by elevated fasting plasma glucose and insulin levels, increased homeostatic model assessment for insulin resistance, and glucose intolerance that was blunted in ECCD36-/- mice. Improved insulin sensitivity in ECCD36-/- mice was characterized by increased phosphoinositide 3-kinases/protein kinase B signaling that further augmented glucose transporter type 4 expression and glucose uptake. Meanwhile, 16 wk of WD feeding also increased skeletal muscle free fatty acid (FFA) and lipid accumulation, without any observed changes in plasma FFA levels. These lipid metabolic disorders were blunted in ECCD36-/- mice. Moreover, ECCD36 also mediated in vitro palmitic acid-induced lipid accumulation in cultured ECs, subsequently leading to the release of FFAs into the culture media. Furthermore, consumption of a WD increased FFA oxidation, mitochondrial dysfunction, impaired mitochondrial respiratory, skeletal muscle fiber type transition, and fibrosis. These WD-induced abnormalities were blunted in ECCD36-/- mice. These findings demonstrate that endothelial-specific ECCD36 signaling participates in skeletal muscle FFA uptake, ectopic lipid accumulation, mitochondrial dysfunction, insulin resistance, and associated skeletal muscle dysfunction in diet-induced obesity.NEW & NOTEWORTHY ECCD36 exerts "extra endothelial cell" actions in skeletal muscle insulin resistance. ECCD36 is a major mediator of Western diet-induced lipid metabolic disorders and insulin resistance in skeletal muscle. Mitochondrial dysfunction is associated with diet-induced CD36 activation and related skeletal muscle insulin resistance.
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Affiliation(s)
- Austin Dada
- Department of Medicine-Endocrinology and Metabolism, University of Missouri School of Medicine, Columbia, Missouri, United States
| | - Javad Habibi
- Department of Medicine-Endocrinology and Metabolism, University of Missouri School of Medicine, Columbia, Missouri, United States
- Research Service, Harry S Truman Memorial Veterans Hospital, Research Service, Columbia, Missouri, United States
| | - Huma Naz
- Department of Medicine-Endocrinology and Metabolism, University of Missouri School of Medicine, Columbia, Missouri, United States
- Research Service, Harry S Truman Memorial Veterans Hospital, Research Service, Columbia, Missouri, United States
| | - Dongqing Chen
- Department of Medicine-Endocrinology and Metabolism, University of Missouri School of Medicine, Columbia, Missouri, United States
- Research Service, Harry S Truman Memorial Veterans Hospital, Research Service, Columbia, Missouri, United States
| | - Guido Lastra
- Department of Medicine-Endocrinology and Metabolism, University of Missouri School of Medicine, Columbia, Missouri, United States
- Research Service, Harry S Truman Memorial Veterans Hospital, Research Service, Columbia, Missouri, United States
| | - Brian P Bostick
- Department of Medicine-Cardiovascular Medicine, University of Missouri School of Medicine, Columbia, Missouri, United States
| | - Adam Whaley-Connell
- Department of Medicine-Endocrinology and Metabolism, University of Missouri School of Medicine, Columbia, Missouri, United States
- Research Service, Harry S Truman Memorial Veterans Hospital, Research Service, Columbia, Missouri, United States
- Department of Medicine-Nephrology and Hypertension, University of Missouri School of Medicine, Columbia, Missouri, United States
| | - Michael A Hill
- Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri, United States
- Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, United States
| | - James R Sowers
- Department of Medicine-Endocrinology and Metabolism, University of Missouri School of Medicine, Columbia, Missouri, United States
- Research Service, Harry S Truman Memorial Veterans Hospital, Research Service, Columbia, Missouri, United States
- Department of Medicine-Cardiovascular Medicine, University of Missouri School of Medicine, Columbia, Missouri, United States
- Department of Medicine-Nephrology and Hypertension, University of Missouri School of Medicine, Columbia, Missouri, United States
- Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri, United States
- Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, United States
| | - Guanghong Jia
- Department of Medicine-Endocrinology and Metabolism, University of Missouri School of Medicine, Columbia, Missouri, United States
- Research Service, Harry S Truman Memorial Veterans Hospital, Research Service, Columbia, Missouri, United States
- Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, United States
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Palatnik A, Feghali MN. From Standard of Care to Emerging Innovations: Navigating the Evolution of Pharmacological Treatment of Gestational Diabetes. Am J Perinatol 2024:10.1055/a-2407-0905. [PMID: 39333039 PMCID: PMC11946926 DOI: 10.1055/a-2407-0905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/29/2024]
Abstract
The incidence of gestational diabetes mellitus (GDM) continues to increase in the United States and globally. While the first-line treatment of GDM remains diet and exercise, 30% of patients with GDM will require pharmacotherapy. However, many controversies remain over the specific glycemic threshold values at which pharmacotherapy should be started, how intensified the therapy should be, and whether oral agents are effective in GDM and remain safe for long-term offspring health. This review will summarize recently completed and ongoing trials focused on GDM pharmacotherapy, including those examining different glycemic thresholds to initiate therapy and treatment intensity. KEY POINTS: · The incidence of GDM continues to increase in the United States and globally.. · While the first-line treatment of GDM remains diet, 30% of patients require pharmacotherapy.. · Controversies remain over the specific glycemic threshold values at which pharmacotherapy is needed.. · Another controversy is how tightly to control GDM.. · Additional controversies are the safety of metformin and incretins in terms of offspring's long-term health..
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Affiliation(s)
- Anna Palatnik
- Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine Medical College of Wisconsin, Milwaukee, WI
- Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI
| | - Maisa N Feghali
- Department of Obstetrics, Gynecology and Reproductive Sciences, Magee Women’s Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA
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Nair S, Razo-Azamar M, Jayabalan N, Dalgaard LT, Palacios-González B, Sørensen A, Kampmann U, Handberg A, Carrion F, Salomon C. Advances in extracellular vesicles as mediators of cell-to-cell communication in pregnancy. Cytokine Growth Factor Rev 2024; 76:86-98. [PMID: 38233286 DOI: 10.1016/j.cytogfr.2023.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 12/27/2023] [Indexed: 01/19/2024]
Abstract
Cell-to-cell communication mediated by Extracellular Vesicles (EVs) is a novel and emerging area of research, especially during pregnancy, in which placenta derived EVs can facilitate the feto-maternal communication. EVs comprise a heterogeneous group of vesicle sub-populations with diverse physical and biochemical characteristics and originate by specific biogenesis mechanisms. EVs transfer molecular cargo (including proteins, nucleic acids, and lipids) between cells and are critical mediators of cell communication. There is growing interest among researchers to explore into the molecular cargo of EVs and their functions in a physiological and pathological context. For example, inflammatory mediators such as cytokines are shown to be released in EVs and EVs derived from immune cells play key roles in mediating the immune response as well as immunoregulatory pathways. Pregnancy complications such as gestational diabetes mellitus, preeclampsia, intrauterine growth restriction and preterm birth are associated with altered levels of circulating EVs, with differential EV cargo and bioactivity in target cells. This implicates the intriguing roles of EVs in reprogramming the maternal physiology during pregnancy. Moreover, the capacity of EVs to carry bioactive molecules makes them a promising tool for biomarker development and targeted therapies in pregnancy complications. This review summarizes the physiological and pathological roles played by EVs in pregnancy and pregnancy-related disorders and describes the potential of EVs to be translated into clinical applications in the diagnosis and treatment of pregnancy complications.
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Affiliation(s)
- Soumyalekshmi Nair
- Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group, University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4029, Australia.
| | - Melissa Razo-Azamar
- Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group, University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4029, Australia; Laboratorio de Envejecimiento Saludable del Instituto Nacional de Medicina Genómica (INMEGEN) en el Centro de Investigación sobre Envejecimiento (CIE-CINVESTAV Sede Sur), CDMX, 14330, Mexico
| | - Nanthini Jayabalan
- Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group, University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4029, Australia
| | | | - Berenice Palacios-González
- Laboratorio de Envejecimiento Saludable del Instituto Nacional de Medicina Genómica (INMEGEN) en el Centro de Investigación sobre Envejecimiento (CIE-CINVESTAV Sede Sur), CDMX, 14330, Mexico
| | - Anne Sørensen
- Department of Obstetrics and Gynecology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Ulla Kampmann
- Steno Diabetes Center Aarhus, Aarhus University Hospital, and Department of Clinical Medicine, Aarhus University, Denmark
| | - Aase Handberg
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
| | - Flavio Carrion
- Departamento de Investigación, Postgrado y Educación Continua (DIPEC), Facultad de Ciencias de la Salud, Universidad del Alba, Santiago, Chile
| | - Carlos Salomon
- Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group, University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4029, Australia; Departamento de Investigación, Postgrado y Educación Continua (DIPEC), Facultad de Ciencias de la Salud, Universidad del Alba, Santiago, Chile.
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Banerjeee S, Adhikary P, Dey BK, Chowdhury S, Bhattacharjee R. Serum BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand) levels in the first trimester may predict the future development of gestational diabetes mellitus. Diabetes Metab Syndr 2024; 18:103019. [PMID: 38653036 DOI: 10.1016/j.dsx.2024.103019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 04/15/2024] [Accepted: 04/16/2024] [Indexed: 04/25/2024]
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) is a prevalent condition with an unclear pathogenesis. B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are potential key players in GDM. PARTICIPANTS, MATERIALS, AND METHODS In a longitudinal observational study, we monitored women from the first trimester through 24-28 weeks of gestation, focusing on the development of GDM. Serum levels of BAFF and APRIL, as well as their mRNA expression, were evaluated in both the first and third trimesters. Furthermore, we assessed cytokines, adipokines, and placental hormones in the serum. RESULTS In the first trimester, participants who later developed GDM exhibited elevated serum BAFF and reduced serum APRIL levels, although the mRNA expression of these molecules was similar to controls. Serum BAFF exhibited significant positive correlations with metabolic markers and placental hormones. Conversely, serum APRIL was negatively correlated with insulin resistance and inflammatory markers but positively correlated with adiponectin. In the early third trimester, GDM participants continued to display higher serum BAFF levels and lower serum APRIL levels than controls. There was no significant difference in mRNA expression of BAFF between GDM and control groups. Conversely, APRIL mRNA expression was significantly lower in the GDM group. The predictive potential of first-trimester BAFF and APRIL levels for future GDM development was explored, with both molecules demonstrating strong predictive capability. DISCUSSION AND CONCLUSION This study suggests that elevated serum BAFF and reduced serum APRIL levels during pregnancy may be associated with the development of GDM. These biomarkers can serve as potential early predictors for GDM.
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Affiliation(s)
- Sudipta Banerjeee
- Department of Endocrinology & Metabolism, IPGME&R and SSKM Hospital, Kolkata, West Bengal, India
| | - Pieu Adhikary
- Department of Endocrinology & Metabolism, IPGME&R and SSKM Hospital, Kolkata, West Bengal, India
| | - Bishal Kumar Dey
- Department of Endocrinology & Metabolism, IPGME&R and SSKM Hospital, Kolkata, West Bengal, India
| | - Subhankar Chowdhury
- Department of Endocrinology & Metabolism, IPGME&R and SSKM Hospital, Kolkata, West Bengal, India
| | - Rana Bhattacharjee
- Department of Endocrinology & Metabolism, IPGME&R and SSKM Hospital, Kolkata, West Bengal, India.
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Xing Y, Wang H, Chao C, Ding X, Li G. Gestational diabetes mellitus in the era of COVID-19: Challenges and opportunities. Diabetes Metab Syndr 2024; 18:102991. [PMID: 38569447 DOI: 10.1016/j.dsx.2024.102991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 03/13/2024] [Accepted: 03/18/2024] [Indexed: 04/05/2024]
Abstract
BACKGROUND AND AIMS The impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnant women, especially those with gestational diabetes mellitus (GDM), has yet to be fully understood. This review aims to examine the interaction between GDM and COVID-19 and to elucidate the pathophysiological mechanisms underlying the comorbidity of these two conditions. METHODS We performed a systematic literature search using the databases of PubMed, Embase, and Web of Science with appropriate keywords and MeSH terms. Our analysis included studies published up to January 26, 2023. RESULTS Despite distinct clinical manifestations, GDM and COVID-19 share common pathophysiological characteristics, which involve complex interactions across multiple organs and systems. On the one hand, infection with severe acute respiratory syndrome coronavirus 2 may target the pancreas and placenta, resulting in β-cell dysfunction and insulin resistance in pregnant women. On the other hand, the hormonal and inflammatory changes that occur during pregnancy could also increase the risk of severe COVID-19 in mothers with GDM. Personalized management and close monitoring are crucial for treating pregnant women with both GDM and COVID-19. CONCLUSIONS A comprehensive understanding of the interactive mechanisms of GDM and COVID-19 would facilitate the initiation of more targeted preventive and therapeutic strategies. There is an urgent need to develop novel biomarkers and functional indicators for early identification and intervention of these conditions.
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Affiliation(s)
- Yuhan Xing
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China; Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Qingdao Women and Children's Hospital, Qingdao University, Qingdao, Shandong Province, China
| | - Hong Wang
- Public Health School, Medical College of Qingdao University, Qingdao, Shandong Province, China
| | - Cong Chao
- Qingdao Women and Children's Hospital, Qingdao University, Qingdao, Shandong Province, China
| | - Xueteng Ding
- Public Health School, Medical College of Qingdao University, Qingdao, Shandong Province, China
| | - Guoju Li
- Qingdao Women and Children's Hospital, Qingdao University, Qingdao, Shandong Province, China.
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Kim CW, Lee JM, Park SW. Divergent roles of the regulatory subunits of class IA PI3K. Front Endocrinol (Lausanne) 2024; 14:1152579. [PMID: 38317714 PMCID: PMC10839044 DOI: 10.3389/fendo.2023.1152579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 12/11/2023] [Indexed: 02/07/2024] Open
Abstract
The regulatory subunit of phosphatidylinositol 3-kinase (PI3K), known as p85, is a critical component in the insulin signaling pathway. Extensive research has shed light on the diverse roles played by the two isoforms of p85, namely p85α and p85β. The gene pik3r1 encodes p85α and its variants, p55α and p50α, while pik3r2 encodes p85β. These isoforms exhibit various activities depending on tissue types, nutrient availability, and cellular stoichiometry. Whole-body or liver-specific deletion of pik3r1 have shown to display increased insulin sensitivity and improved glucose homeostasis; however, skeletal muscle-specific deletion of p85α does not exhibit any significant effects on glucose homeostasis. On the other hand, whole-body deletion of pik3r2 shows improved insulin sensitivity with no significant impact on glucose tolerance. Meanwhile, liver-specific double knockout of pik3r1 and pik3r2 leads to reduced insulin sensitivity and glucose tolerance. In the context of obesity, upregulation of hepatic p85α or p85β has been shown to improve glucose homeostasis. However, hepatic overexpression of p85α in the absence of p50α and p55α results in increased insulin resistance in obese mice. p85α and p85β have distinctive roles in cancer development. p85α acts as a tumor suppressor, but p85β promotes tumor progression. In the immune system, p85α facilitates B cell development, while p85β regulates T cell differentiation and maturation. This review provides a comprehensive overview of the distinct functions attributed to p85α and p85β, highlighting their significance in various physiological processes, including insulin signaling, cancer development, and immune system regulation.
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Affiliation(s)
- Cho-Won Kim
- Division of Endocrinology, Boston Children’s Hospital, Boston, MA, United States
- Department of Pediatrics, Harvard Medical School, Boston, MA, United States
| | - Junsik M. Lee
- Division of Endocrinology, Boston Children’s Hospital, Boston, MA, United States
| | - Sang Won Park
- Division of Endocrinology, Boston Children’s Hospital, Boston, MA, United States
- Department of Pediatrics, Harvard Medical School, Boston, MA, United States
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11
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Qi W, Zhu D, Yin P, Gu X, Zhao Z, Li M, Dong C, Tang Q, Xie W, Zhou T, Xia H, Qiu X, Yang X, Gao G. Pigment Epithelium-Derived Factor, a Novel Adipokine, Contributes to Gestational Diabetes Mellitus. J Clin Endocrinol Metab 2023; 109:e356-e369. [PMID: 37440564 DOI: 10.1210/clinem/dgad413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 07/04/2023] [Accepted: 07/10/2023] [Indexed: 07/15/2023]
Abstract
CONTEXT Excessive insulin resistance, inadequate insulin compensation, or both could result in gestational diabetes mellitus (GDM). Levels of pigment epithelium-derived factor (PEDF), a novel adipokine that could induce insulin resistance, are high in patients with obesity and diabetes. However, the impact of PEDF in pregnancy remains unknown. OBJECTIVE This study aimed to elucidate the role of PEDF on insulin resistance and compensatory elevation of insulin levels during normal pregnancy and in patients with GDM. METHODS In this population-based and cohort study, logistic regression analysis was performed to determine the association of PEDF/adiponectin/leptin levels with the risk of developing GDM and to predict postpartum prediabetes. PEDF protein, PEDF transgenic mice, PEDF knockout mice, and PEDF-neutralized antibodies were used to observe changes in insulin resistance and insulin levels with pregnancy. RESULTS Plasma PEDF levels were increased in normal pregnancy and higher in GDM women. Higher PEDF levels were associated with the increased risk of developing GDM and emerged as a significant independent determinant of postpartum prediabetes in GDM women. Mechanistically, in vivo and in vitro experiments revealed that PEDF induced insulin resistance by inhibiting the insulin signaling pathway. CONCLUSION In addition to insulin resistance and upregulated insulin levels in normal pregnancy and GDM, aberrant PEDF levels can serve as a "fingerprint" of metabolic abnormalities during pregnancy. Thus, PEDF is a valuable biomarker but could interfere with the time course for early diagnosis and prognosis of GDM.
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Affiliation(s)
- Weiwei Qi
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
| | - Dan Zhu
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
| | - Ping Yin
- Department of Clinical Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China
| | - Xiaoqiong Gu
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China
| | - Zhen Zhao
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
| | - Miaoxin Li
- Center for Precision Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
| | - Chang Dong
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
| | - Qilong Tang
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
| | - Wanting Xie
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
| | - Ti Zhou
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
| | - Huimin Xia
- Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China
| | - Xiu Qiu
- Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China
| | - Xia Yang
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
- Guangdong Engineering & Technology Research Center for Gene Manipulation and Biomacromolecular Products, Sun Yat-sen University, Guangzhou, China
| | - Guoquan Gao
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
- Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
- Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, China
- Guangdong Provincial Key Laboratory of Diabetology& Guangzhou Municipal Key Laboratory of Mechanistic and Translational Obesity Research, Medical Center for Comprehensive Weight Control, The Third Affiliated Hospital of Sun Yat-sen University Guangzhou, Guangdong, China
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12
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Tocci V, Mirabelli M, Salatino A, Sicilia L, Giuliano S, Brunetti FS, Chiefari E, De Sarro G, Foti DP, Brunetti A. Metformin in Gestational Diabetes Mellitus: To Use or Not to Use, That Is the Question. Pharmaceuticals (Basel) 2023; 16:1318. [PMID: 37765126 PMCID: PMC10537239 DOI: 10.3390/ph16091318] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 09/12/2023] [Accepted: 09/15/2023] [Indexed: 09/29/2023] Open
Abstract
In recent years, there has been a dramatic increase in the number of pregnancies complicated by gestational diabetes mellitus (GDM). GDM occurs when maternal insulin resistance develops and/or progresses during gestation, and it is not compensated by a rise in maternal insulin secretion. If not properly managed, this condition can cause serious short-term and long-term problems for both mother and child. Lifestyle changes are the first line of treatment for GDM, but if ineffective, insulin injections are the recommended pharmacological treatment choice. Some guidance authorities and scientific societies have proposed the use of metformin as an alternative pharmacological option for treating GDM, but there is not yet a unanimous consensus on this. Although the use of metformin appears to be safe for the mother, concerns remain about its long-term metabolic effects on the child that is exposed in utero to the drug, given that metformin, contrary to insulin, crosses the placenta. This review article describes the existing lines of evidence about the use of metformin in pregnancies complicated by GDM, in order to clarify its potential benefits and limits, and to help clinicians make decisions about who could benefit most from this drug treatment.
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Affiliation(s)
- Vera Tocci
- Department of Health Sciences, University “Magna Græcia” of Catanzaro, 88100 Catanzaro, Italy; (V.T.); (M.M.)
- Operative Unit of Endocrinology, Diabetes in Pregnancy Ambulatory Care Center, Renato Dulbecco University Hospital, 88100 Catanzaro, Italy
| | - Maria Mirabelli
- Department of Health Sciences, University “Magna Græcia” of Catanzaro, 88100 Catanzaro, Italy; (V.T.); (M.M.)
- Operative Unit of Endocrinology, Diabetes in Pregnancy Ambulatory Care Center, Renato Dulbecco University Hospital, 88100 Catanzaro, Italy
| | - Alessandro Salatino
- Department of Health Sciences, University “Magna Græcia” of Catanzaro, 88100 Catanzaro, Italy; (V.T.); (M.M.)
| | - Luciana Sicilia
- Operative Unit of Endocrinology, Diabetes in Pregnancy Ambulatory Care Center, Renato Dulbecco University Hospital, 88100 Catanzaro, Italy
| | - Stefania Giuliano
- Operative Unit of Endocrinology, Diabetes in Pregnancy Ambulatory Care Center, Renato Dulbecco University Hospital, 88100 Catanzaro, Italy
| | - Francesco S. Brunetti
- Department of Health Sciences, University “Magna Græcia” of Catanzaro, 88100 Catanzaro, Italy; (V.T.); (M.M.)
| | - Eusebio Chiefari
- Department of Health Sciences, University “Magna Græcia” of Catanzaro, 88100 Catanzaro, Italy; (V.T.); (M.M.)
| | - Giovambattista De Sarro
- Department of Health Sciences, University “Magna Græcia” of Catanzaro, 88100 Catanzaro, Italy; (V.T.); (M.M.)
| | - Daniela P. Foti
- Department of Experimental and Clinical Medicine, University “Magna Græcia” of Catanzaro, 88100 Catanzaro, Italy;
| | - Antonio Brunetti
- Department of Health Sciences, University “Magna Græcia” of Catanzaro, 88100 Catanzaro, Italy; (V.T.); (M.M.)
- Operative Unit of Endocrinology, Diabetes in Pregnancy Ambulatory Care Center, Renato Dulbecco University Hospital, 88100 Catanzaro, Italy
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13
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Sakr HF, Sirasanagandla SR, Das S, Bima AI, Elsamanoudy AZ. Insulin Resistance and Hypertension: Mechanisms Involved and Modifying Factors for Effective Glucose Control. Biomedicines 2023; 11:2271. [PMID: 37626767 PMCID: PMC10452601 DOI: 10.3390/biomedicines11082271] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Revised: 07/18/2023] [Accepted: 08/01/2023] [Indexed: 08/27/2023] Open
Abstract
Factors such as aging, an unhealthy lifestyle with decreased physical activity, snacking, a standard Western diet, and smoking contribute to raising blood pressure to a dangerous level, increasing the risk of coronary artery disease and heart failure. Atherosclerosis, or aging of the blood vessels, is a physiological process that has accelerated in the last decades by the overconsumption of carbohydrates as the primary sources of caloric intake, resulting in increased triglycerides and VLDL-cholesterol and insulin spikes. Classically, medications ranging from beta blockers to angiotensin II blockers and even calcium channel blockers were used alone or in combination with lifestyle modifications as management tools in modern medicine to control arterial blood pressure. However, it is not easy to control blood pressure or the associated complications. A low-carbohydrate, high-fat (LCHF) diet can reduce glucose and insulin spikes, improve insulin sensitivity, and lessen atherosclerosis risk factors. We reviewed articles describing the etiology of insulin resistance (IR) and its impact on arterial blood pressure from databases including PubMed, PubMed Central, and Google Scholar. We discuss how the LCHF diet is beneficial to maintaining arterial blood pressure at normal levels, slowing down the progression of atherosclerosis, and reducing the use of antihypertensive medications. The mechanisms involved in IR associated with hypertension are also highlighted.
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Affiliation(s)
- Hussein F. Sakr
- Department of Physiology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Srinivasa Rao Sirasanagandla
- Department of Human and Clinical Anatomy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman; (S.R.S.); (S.D.)
| | - Srijit Das
- Department of Human and Clinical Anatomy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman; (S.R.S.); (S.D.)
| | - Abdulhadi I. Bima
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21465, Saudi Arabia; (A.I.B.); (A.Z.E.)
| | - Ayman Z. Elsamanoudy
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21465, Saudi Arabia; (A.I.B.); (A.Z.E.)
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14
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Piotrowska K, Zgutka K, Tkacz M, Tarnowski M. Physical Activity as a Modern Intervention in the Fight against Obesity-Related Inflammation in Type 2 Diabetes Mellitus and Gestational Diabetes. Antioxidants (Basel) 2023; 12:1488. [PMID: 37627482 PMCID: PMC10451679 DOI: 10.3390/antiox12081488] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 07/18/2023] [Accepted: 07/21/2023] [Indexed: 08/27/2023] Open
Abstract
Diabetes is one of the greatest healthcare problems; it requires an appropriate approach to the patient, especially when it concerns pregnant women. Gestational diabetes mellitus (GDM) is a common metabolic condition in pregnancy that shares many features with type 2 diabetes mellitus (T2DM). T2DM and GDM induce oxidative stress, which activates cellular stress signalling. In addition, the risk of diabetes during pregnancy can lead to various complications for the mother and foetus. It has been shown that physical activity is an important tool to not only treat the negative effects of diabetes but also to prevent its progression or even reverse the changes already made by limiting the inflammatory process. Physical activity has a huge impact on the immune status of an individual. Various studies have shown that regular training sessions cause changes in circulating immune cell levels, cytokine activation, production and secretion and changes in microRNA, all of which have a positive effect on the well-being of the diabetic patient, mother and foetus.
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Affiliation(s)
- Katarzyna Piotrowska
- Department of Physiology, Pomeranian Medical University in Szczecin, al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland
| | - Katarzyna Zgutka
- Department of Physiology in Health Sciences, Faculty of Health Sciences, Pomeranian Medical University in Szczecin, Zolnierska 54, 70-210 Szczecin, Poland
| | - Marta Tkacz
- Department of Physiology in Health Sciences, Faculty of Health Sciences, Pomeranian Medical University in Szczecin, Zolnierska 54, 70-210 Szczecin, Poland
| | - Maciej Tarnowski
- Department of Physiology in Health Sciences, Faculty of Health Sciences, Pomeranian Medical University in Szczecin, Zolnierska 54, 70-210 Szczecin, Poland
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15
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Sharma AK, Singh S, Singh H, Mahajan D, Kolli P, Mandadapu G, Kumar B, Kumar D, Kumar S, Jena MK. Deep Insight of the Pathophysiology of Gestational Diabetes Mellitus. Cells 2022; 11:2672. [PMID: 36078079 PMCID: PMC9455072 DOI: 10.3390/cells11172672] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 08/22/2022] [Accepted: 08/23/2022] [Indexed: 12/19/2022] Open
Abstract
Diabetes mellitus is a severe metabolic disorder, which consistently requires medical care and self-management to restrict complications, such as obesity, kidney damage and cardiovascular diseases. The subtype gestational diabetes mellitus (GDM) occurs during pregnancy, which severely affects both the mother and the growing foetus. Obesity, uncontrolled weight gain and advanced gestational age are the prominent risk factors for GDM, which lead to high rate of perinatal mortality and morbidity. In-depth understanding of the molecular mechanism involved in GDM will help researchers to design drugs for the optimal management of the condition without affecting the mother and foetus. This review article is focused on the molecular mechanism involved in the pathophysiology of GDM and the probable biomarkers, which can be helpful for the early diagnosis of the condition. The early diagnosis of the metabolic disorder, most preferably in first trimester of pregnancy, will lead to its effective long-term management, reducing foetal developmental complications and mortality along with safety measures for the mother.
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Affiliation(s)
- Amarish Kumar Sharma
- Department of Biotechnology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, Punjab, India
| | - Sanjeev Singh
- Department of Biotechnology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, Punjab, India
| | - Himanshu Singh
- Department of Biotechnology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, Punjab, India
| | - Deviyani Mahajan
- Department of Biotechnology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, Punjab, India
| | - Prachetha Kolli
- Microgen Health Inc., 14225 Sullyfield Cir Suite E, Chantilly, VA 20151, USA
| | | | - Bimlesh Kumar
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India
| | - Dharmendra Kumar
- Animal Physiology and Reproduction Division, ICAR-Central Institute for Research on Buffaloes, Hisar 125001, Haryana, India
| | - Sudarshan Kumar
- Animal Biotechnology Centre, ICAR-National Dairy Research Institute, Karnal 132001, Haryana, India
| | - Manoj Kumar Jena
- Department of Biotechnology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, Punjab, India
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16
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Tamas I, Major E, Horvath D, Keller I, Ungvari A, Haystead TA, MacDonald JA, Lontay B. Mechanisms by which smoothelin-like protein 1 reverses insulin resistance in myotubules and mice. Mol Cell Endocrinol 2022; 551:111663. [PMID: 35508278 DOI: 10.1016/j.mce.2022.111663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 04/27/2022] [Accepted: 04/27/2022] [Indexed: 10/18/2022]
Abstract
Insulin resistance (InR) is manifested in skeletal muscle by decreased insulin-stimulated glucose uptake due to impaired insulin signaling and multiple post-receptor intracellular defects. Chronic glucose-induced insulin resistance leads to the activation of Ser/Thr kinases and elevated phosphorylation of insulin receptor substrate 1 (IRS1) on Ser residues. Phosphorylation of IRS1 triggers the dissociation of IRS1 and its downstream effector, phosphatidylinositol 3-kinase. In the present study, we provide evidence for the insulin-sensitizing role of smoothelin-like protein 1 (SMTNL1) that is a ligand-dependent co-regulator of steroid receptors, predominantly the progesterone receptor. SMTNL1 was transiently overexpressed in insulin-resistant C2C12 myotubes. A proteome profiler array revealed that mTOR and Ser/Thr kinases were SMTNL1-dependent signaling pathways. In the presence of progesterone, overexpression was coupled to decreased Ser phosphorylation of IRS1 at Ser307, Ser318, and Ser612 residues. SMTNL1 also induced the expression and activity of the p85 subunit of PI3K. SMTNL1 regulated the expression of PKCε, which phosphorylates IRS1 at Ser318 residue. SMTNL1 also regulated ERK1/2 and JNK, which phosphorylate IRS1 at Ser612 and Ser307, respectively. Real-time metabolic measurements of oxygen consumption rate and extracellular acidification rate revealed that SMTNL1 improved glycolysis and promoted the utilization of alternative carbon fuels. SMTNL1 also rescued the mitochondrial respiration defect induced by chronic insulin exposure. Collectively, SMTNL1 plays a crucial role in maintaining the physiological ratio of Tyr/Ser IRS1 phosphorylation and attenuates the insulin-signaling cascade that contributes to impaired glucose disposal, which makes it a potential therapeutic target for improving InR.
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Affiliation(s)
- Istvan Tamas
- Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Evelin Major
- Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Daniel Horvath
- Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Ilka Keller
- Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Adam Ungvari
- Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Timothy A Haystead
- Duke University School of Medicine, Department of Pharmacology and Cancer Biology, Durham, NC, USA
| | - Justin A MacDonald
- Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Beata Lontay
- Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
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17
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The newborn metabolome: associations with gestational diabetes, sex, gestation, birth mode, and birth weight. Pediatr Res 2022; 91:1864-1873. [PMID: 34526650 DOI: 10.1038/s41390-021-01672-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 07/07/2021] [Accepted: 07/14/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Pathways towards many adult-onset conditions begin early in life, even in utero. Maternal health in pregnancy influences this process, but little is known how it affects neonatal metabolism. We investigated associations between pregnancy and birth factors and cord blood metabolomic profile in a large, population-derived cohort. METHODS Metabolites were measured using nuclear magnetic resonance in maternal (28 weeks gestation) and cord serum from 912 mother-child pairs in the Barwon Infant Study pre-birth cohort. Associations between maternal (metabolites, age, BMI, smoking), pregnancy (pre-eclampsia, gestational diabetes (GDM)), and birth characteristics (delivery mode, gestational age, weight, infant sex) with 72 cord blood metabolites were examined by linear regression. RESULTS Delivery mode, sex, gestational age, and birth weight were associated with specific metabolite levels in cord blood, including amino acids, fatty acids, and cholesterols. GDM was associated with higher cord blood levels of acetoacetate and 3-hydroxybutyrate. CONCLUSIONS Neonatal factors, particularly delivery mode, were associated with many cord blood metabolite differences, including those implicated in later risk of cardiometabolic disease. Associations between GDM and higher offspring ketone levels at birth are consistent with maternal ketosis in diabetic pregnancies. Further work is needed to determine whether these neonatal metabolome differences associate with later health outcomes. IMPACT Variations in blood metabolomic profile have been linked to health status in adults and children, but corresponding data in neonates are scarce. We report evidence that pregnancy complications, mode of delivery, and offspring characteristics, including sex, are independently associated with a range of circulating metabolites at birth, including ketone bodies, amino acids, cholesterols, and inflammatory markers. Independent of birth weight, exposure to gestational diabetes is associated with higher cord blood ketone bodies and citrate. These findings suggest that pregnancy complications, mode of delivery, gestational age, and measures of growth influence metabolic pathways prior to birth, potentially impacting later health and development.
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18
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Chatterjee B, Neelaveni K, Kenchey H, Thakur SS. An insight into major signaling pathways and protein-protein interaction networks involved in the pathogenesis of gestational diabetes mellitus. Proteomics 2022; 22:e2100200. [PMID: 35279034 DOI: 10.1002/pmic.202100200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 02/28/2022] [Accepted: 03/04/2022] [Indexed: 11/11/2022]
Abstract
Gestational diabetes mellitus (GDM) is associated with the increase of glucose in the blood rather than being absorbed by the cells. A better understanding of the signaling pathways is necessary to understand the pathophysiology of GDM. This study provides details about a series of signaling pathways and protein-protein interactions involved in the pathogenesis of GDM and their evaluations in GDM development. Protein-protein interactions were found between proteins of several signaling pathways that suggest interlink between these signaling pathways. Protein-protein interactions were generated with high confidence interaction scores based on textmining, co-occurrence, coexpression, neighborhood, gene fusion, experiments and databases. The dysregulation of signaling pathways may also contribute to the increased risk of complications associated with GDM in the mother and child. Further, studies on signaling pathways involved in the pathogenesis of GDM would help in the development of an effective intervention to prevent GDM along with the identification of key targets for effective therapies in the future. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Bhaswati Chatterjee
- National Institute of Pharmaceutical Education and Research, Hyderabad, India
| | | | - Himaja Kenchey
- Institute of Diabetes, Endocrinology and Adiposity Clinics, Hyderabad, India
| | - Suman S Thakur
- Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, India
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19
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Zhang YP, Ye SZ, Li YX, Chen JL, Zhang YS. Research Advances in the Roles of Circular RNAs in Pathophysiology and Early Diagnosis of Gestational Diabetes Mellitus. Front Cell Dev Biol 2022; 9:739511. [PMID: 35059395 PMCID: PMC8764237 DOI: 10.3389/fcell.2021.739511] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 12/02/2021] [Indexed: 11/30/2022] Open
Abstract
Gestational diabetes mellitus (GDM) refers to different degrees of glucose tolerance abnormalities that occur during pregnancy or are discovered for the first time, which can have a serious impact on the mother and the offspring. The screening of GDM mainly relies on the oral glucose tolerance test (OGTT) at 24–28 weeks of gestation. The early diagnosis and intervention of GDM can greatly improve adverse pregnancy outcomes. However, molecular markers for early prediction and diagnosis of GDM are currently lacking. Therefore, looking for GDM-specific early diagnostic markers has important clinical significance for the prevention and treatment of GDM and the management of subsequent maternal health. Circular RNA (circRNA) is a new type of non-coding RNA. Recent studies have found that circRNAs were involved in the occurrence and development of malignant tumors, metabolic diseases, cardiovascular and cerebrovascular diseases, etc., and could be used as the molecular marker for early diagnosis. Our previous research showed that circRNAs are differentially expressed in serum of GDM pregnant women in the second and third trimester, placental tissues during cesarean delivery, and cord blood. However, the mechanism of circular RNA in GDM still remains unclear. This article focuses on related circRNAs involved in insulin resistance and β-cell dysfunction, speculating on the possible role of circRNAs in the pathophysiology of GDM under the current research context, and has the potential to serve as early molecular markers for the diagnosis of GDM.
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Affiliation(s)
- Yan-Ping Zhang
- The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China.,Medical School, Ningbo University, Ningbo, China
| | - Sha-Zhou Ye
- Translational Research Laboratory for Urology, the Key Laboratory of Ningbo City, Ningbo First Hospital, Ningbo, China
| | - Ying-Xue Li
- Medical School, Ningbo University, Ningbo, China
| | - Jia-Li Chen
- Medical School, Ningbo University, Ningbo, China
| | - Yi-Sheng Zhang
- The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China
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20
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Furigo IC, Dearden L. Mechanisms mediating the impact of maternal obesity on offspring hypothalamic development and later function. Front Endocrinol (Lausanne) 2022; 13:1078955. [PMID: 36619540 PMCID: PMC9813846 DOI: 10.3389/fendo.2022.1078955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 12/06/2022] [Indexed: 12/24/2022] Open
Abstract
As obesity rates have risen around the world, so to have pregnancies complicated by maternal obesity. Obesity during pregnancy is not only associated with negative health outcomes for the mother and the baby during pregnancy and birth, there is also strong evidence that exposure to maternal obesity causes an increased risk to develop obesity, diabetes and cardiovascular disease later in life. Animal models have demonstrated that increased weight gain in offspring exposed to maternal obesity is usually preceded by increased food intake, implicating altered neuronal control of food intake as a likely area of change. The hypothalamus is the primary site in the brain for maintaining energy homeostasis, which it coordinates by sensing whole body nutrient status and appropriately adjusting parameters including food intake. The development of the hypothalamus is plastic and regulated by metabolic hormones such as leptin, ghrelin and insulin, making it vulnerable to disruption in an obese in utero environment. This review will summarise how the hypothalamus develops, how maternal obesity impacts on structure and function of the hypothalamus in the offspring, and the factors that are altered in an obese in utero environment that may mediate the permanent changes to hypothalamic function in exposed individuals.
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Affiliation(s)
- Isadora C. Furigo
- Centre for Sport, Exercise and Life Sciences, School of Life Sciences, Coventry University, Coventry, United Kingdom
| | - Laura Dearden
- Metabolic Research Laboratories, Wellcome MRC Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
- *Correspondence: Laura Dearden,
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21
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Espinoza C, Fuenzalida B, Leiva A. Increased Fetal Cardiovascular Disease Risk: Potential Synergy Between Gestational Diabetes Mellitus and Maternal Hypercholesterolemia. Curr Vasc Pharmacol 2021; 19:601-623. [PMID: 33902412 DOI: 10.2174/1570161119666210423085407] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 01/27/2021] [Accepted: 03/16/2021] [Indexed: 01/25/2023]
Abstract
Cardiovascular diseases (CVD) remain a major cause of death worldwide. Evidence suggests that the risk for CVD can increase at the fetal stages due to maternal metabolic diseases, such as gestational diabetes mellitus (GDM) and maternal supraphysiological hypercholesterolemia (MSPH). GDM is a hyperglycemic, inflammatory, and insulin-resistant state that increases plasma levels of free fatty acids and triglycerides, impairs endothelial vascular tone regulation, and due to the increased nutrient transport, exposes the fetus to the altered metabolic conditions of the mother. MSPH involves increased levels of cholesterol (mainly as low-density lipoprotein cholesterol) which also causes endothelial dysfunction and alters nutrient transport to the fetus. Despite that an association has already been established between MSPH and increased CVD risk, however, little is known about the cellular processes underlying this relationship. Our knowledge is further obscured when the simultaneous presentation of MSPH and GDM takes place. In this context, GDM and MSPH may substantially increase fetal CVD risk due to synergistic impairment of placental nutrient transport and endothelial dysfunction. More studies on the separate and/or cumulative role of both processes are warranted to suggest specific treatment options.
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Affiliation(s)
- Cristian Espinoza
- Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Santiago 8330024, Chile
| | - Barbara Fuenzalida
- Institute of Biochemistry and Molecular Medicine, University of Bern, CH-3012 Bern, Switzerland
| | - Andrea Leiva
- School of Medical Technology, Health Sciences Faculty, Universidad San Sebastian, Providencia 7510157, Chile
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22
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Sultan S, Ahmed F, Bajouh O, Schulten HJ, Bagatian N, Al-Dayini R, Subhi O, Karim S, Almalki S. Alterations of transcriptome expression, cell cycle, and mitochondrial superoxide reveal foetal endothelial dysfunction in Saudi women with gestational diabetes mellitus. Endocr J 2021; 68:1067-1079. [PMID: 33867398 DOI: 10.1507/endocrj.ej21-0189] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Gestational diabetes mellitus (GDM) affects one in four Saudi women and is associated with high risks of cardiovascular diseases in both the mother and foetus. It is believed that endothelial cells (ECs) dysfunction initiates these diabetic complications. In this study, differences in the transcriptome profiles, cell cycle distribution, and mitochondrial superoxide (MTS) between human umbilical vein endothelial cells (HUVECs) from GDM patients and those from healthy (control) subjects were analysed. Transcriptome profiles were generated using high-density expression microarray. The selected four altered genes were validated using qRT-PCR. MTS and cell cycle were analysed by flow cytometry. A total of 84 altered genes were identified, comprising 52 upregulated and 32 downregulated genes in GDM.HUVECs. Our selection of the four interested altered genes (TGFB2, KITLG, NEK7, and IGFBP5) was based on the functional network analysis, which revealed that these altered genes are belonging to the highest enrichment score associated with cellular function and proliferation; all of which may contribute to ECs dysfunction. The cell cycle revealed an increased percentage of cells in the G2/M phase in GDM.HUVECs, indicating cell cycle arrest. In addition, we found that GDM.HUVECs had increased MTS generation. In conclusion, GDM induces persistent impairment of the biological functions of foetal ECs, as evidenced by analyses of transcriptome profiles, cell cycle, and MTS even after ECs culture in vitro for several passages under normal glucose conditions.
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Affiliation(s)
- Samar Sultan
- Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Farid Ahmed
- Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Osama Bajouh
- Department of Obstetrics and Gynaecology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Centre of Innovation in Personalized Medicine, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hans-Juergen Schulten
- Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Nadia Bagatian
- Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Roaa Al-Dayini
- Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ohoud Subhi
- Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Sajjad Karim
- Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Sultanah Almalki
- Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
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23
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Wang C, Ren L, Chen S, Zheng H, Yang Y, Gu T, Li Y, Wang C. Longdan Xiegan Tang attenuates liver injury and hepatic insulin resistance by regulating the angiotensin-converting enzyme 2/Ang (1-7)/Mas axis-mediated anti-inflammatory pathway in rats. JOURNAL OF ETHNOPHARMACOLOGY 2021; 274:114072. [PMID: 33781876 DOI: 10.1016/j.jep.2021.114072] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 03/14/2021] [Accepted: 03/22/2021] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The ancient Chinese herbal formula Longdan Xiegan Tang (LXT, also called Gentiana Longdancao Decoction to Drain the Liver) treats insulin resistance- and inflammation-associated liver injuries in clinical practice. AIM OF THE STUDY To investigate the molecular mechanisms underlying LXT-elicited improvement of the liver injuries. MATERIALS AND METHODS Male rats were co-treated with olanzapine (5 mg/kg) and LXT extract (50 and 500 mg/kg) for eight weeks. Blood parameters were determined enzymatically or by ELISA. Gene/protein expression was analyzed by Real-Time PCR, Western blot and/or immunohistochemistry. RESULTS LXT attenuated olanzapine-induced liver injury manifested by hyperactivities of plasma alanine aminotransferase and aspartate aminostransferase, hyperbilirubinemia and hypoalbuminemia. Furthermore, LXT improved hepatic insulin resistance that was indicated by hyperinsulinemia, the increased HOMA-IR index, and hepatic over-phosphorylation of Ser307 in insulin receptor substrate (IRS)1, Ser731 in IRS2, Tyr607 in phosphoinositide 3-kinase p85α and Ser473 in AKT at baseline. Mechanistically, LXT inhibited olanzapine-triggered hepatic over-phosphorylation of both IκB kinase (IKK)α/β and nuclear factor (NF)κB p65 proteins, and mRNA overexpression of tumor necrosis factor α, interleukin 6, interleukin 1β and CD68. More importantly, LXT restored the decreases in angiotensin-converting enzyme 2 (ACE2) protein level, and its downstream targets Ang (1-7) content and Mas receptor expression. CONCLUSIONS The present results demonstrate that LXT attenuates liver injury and hepatic insulin resistance by regulating the ACE2/Ang (1-7)/Mas axis-mediated anti-inflammatory pathway in rats. Our findings provide a better understanding of LXT for treatment of insulin resistance- and inflammation-associated liver injuries.
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Affiliation(s)
- Chengliang Wang
- Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
| | - Liying Ren
- Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Shankang Chen
- Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Huihui Zheng
- Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Yifan Yang
- Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, NSW 2000, Australia.
| | - Tieguang Gu
- Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, NSW 2000, Australia.
| | - Yuhao Li
- Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, NSW 2000, Australia.
| | - Chunxia Wang
- Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
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24
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Alesi S, Ghelani D, Rassie K, Mousa A. Metabolomic Biomarkers in Gestational Diabetes Mellitus: A Review of the Evidence. Int J Mol Sci 2021; 22:ijms22115512. [PMID: 34073737 PMCID: PMC8197243 DOI: 10.3390/ijms22115512] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 05/20/2021] [Accepted: 05/20/2021] [Indexed: 12/14/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is the fastest growing type of diabetes, affecting between 2 to 38% of pregnancies worldwide, varying considerably depending on diagnostic criteria used and sample population studied. Adverse obstetric outcomes include an increased risk of macrosomia, and higher rates of stillbirth, instrumental delivery, and birth trauma. Metabolomics, which is a platform used to analyse and characterise a large number of metabolites, is increasingly used to explore the pathophysiology of cardiometabolic conditions such as GDM. This review aims to summarise metabolomics studies in GDM (from inception to January 2021) in order to highlight prospective biomarkers for diagnosis, and to better understand the dysfunctional metabolic pathways underlying the condition. We found that the most commonly deranged pathways in GDM include amino acids (glutathione, alanine, valine, and serine), carbohydrates (2-hydroxybutyrate and 1,5-anhydroglucitol), and lipids (phosphatidylcholines and lysophosphatidylcholines). We also highlight the possibility of using certain metabolites as predictive markers for developing GDM, with the use of highly stratified modelling techniques. Limitations for metabolomic research are evaluated, and future directions for the field are suggested to aid in the integration of these findings into clinical practice.
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Affiliation(s)
- Simon Alesi
- Monash Centre for Health Research and Implementation (MCHRI), School of Public Health and Preventive Medicine, Monash University, Melbourne 3168, Australia; (S.A.); (D.G.); (K.R.)
| | - Drishti Ghelani
- Monash Centre for Health Research and Implementation (MCHRI), School of Public Health and Preventive Medicine, Monash University, Melbourne 3168, Australia; (S.A.); (D.G.); (K.R.)
| | - Kate Rassie
- Monash Centre for Health Research and Implementation (MCHRI), School of Public Health and Preventive Medicine, Monash University, Melbourne 3168, Australia; (S.A.); (D.G.); (K.R.)
- Department of Diabetes, Monash Health, Melbourne 3168, Australia
| | - Aya Mousa
- Monash Centre for Health Research and Implementation (MCHRI), School of Public Health and Preventive Medicine, Monash University, Melbourne 3168, Australia; (S.A.); (D.G.); (K.R.)
- Correspondence:
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25
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Morosin SK, Lochrin AJ, Delforce SJ, Lumbers ER, Pringle KG. The (pro)renin receptor ((P)RR) and soluble (pro)renin receptor (s(P)RR) in pregnancy. Placenta 2021; 116:43-50. [PMID: 34020806 DOI: 10.1016/j.placenta.2021.04.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 03/31/2021] [Accepted: 04/27/2021] [Indexed: 11/25/2022]
Abstract
The (pro)renin receptor ((P)RR) is a multi-functional protein that can be proteolytically cleaved and released in a soluble form (s(P)RR). Recently, the (P)RR and s(P)RR have become of interest in pregnancy and its associated pathologies. This is because the (P)RR not only activates tissue renin angiotensin systems, but it is also an integral component of vacuolar-ATPase, activates the wingless/integrated (Wnt)/β-catenin and extracellular signal regulated kinases 1 and 2/mitogen-activated protein kinase signalling pathways, and stabilises the β subunit of pyruvate dehydrogenase. Additionally, s(P)RR is detected in plasma and urine, and maternal plasma levels are elevated in pregnancy complications including fetal growth restriction, preeclampsia and gestational diabetes mellitus. Therefore, s(P)RR has potential as a biomarker for these pregnancy pathologies. Preliminary functional findings suggest that s(P)RR may be important for regulating fluid balance, inflammation and blood pressure, all of which contribute to a successful pregnancy. The (P)RR and s(P)RR regulate pathways that are known to be important in maintaining pregnancy, however their role in the physiological context of pregnancy is poorly characterised. This review summarises the known and potential functions of the (P)RR and s(P)RR in pregnancy, and how their dysregulation may contribute to pregnancy complications. It also highlights the need for further research into the source and function of s(P)RR in pregnancy. Soluble (P)RR levels could be indicative of placental, kidney or liver dysfunction and therefore be a novel clinical biomarker, or therapeutic target, to improve the detection and treatment of pregnancy pathologies.
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Affiliation(s)
- Saije K Morosin
- School of Biomedical Sciences and Pharmacy, Priority Research Centre for Reproductive Science, Pregnancy and Reproduction Program, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, 2305, New South Wales, Australia
| | - Alyssa J Lochrin
- School of Biomedical Sciences and Pharmacy, Priority Research Centre for Reproductive Science, Pregnancy and Reproduction Program, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, 2305, New South Wales, Australia
| | - Sarah J Delforce
- School of Biomedical Sciences and Pharmacy, Priority Research Centre for Reproductive Science, Pregnancy and Reproduction Program, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, 2305, New South Wales, Australia
| | - Eugenie R Lumbers
- School of Biomedical Sciences and Pharmacy, Priority Research Centre for Reproductive Science, Pregnancy and Reproduction Program, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, 2305, New South Wales, Australia
| | - Kirsty G Pringle
- School of Biomedical Sciences and Pharmacy, Priority Research Centre for Reproductive Science, Pregnancy and Reproduction Program, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, 2305, New South Wales, Australia.
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26
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Rodríguez-Reyes B, Tufiño C, López Mayorga RM, Mera Jiménez E, Bobadilla Lugo RA. Role of pregnancy on insulin-induced vasorelaxation: the influence of angiotensin II receptors. Can J Physiol Pharmacol 2021; 99:1026-1035. [PMID: 33857388 DOI: 10.1139/cjpp-2021-0057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Insulin resistance is a feature of pregnancy and is associated with increased levels of angiotensin II (Ang II) and insulin. Therefore, pregnancy may change insulin-induced vasodilation through changes in Ang II receptors. Insulin-induced vasorelaxation was evaluated in phenylephrine-precontracted aortic rings of pregnant and non-pregnant rats, using a conventional isolated organ preparation. Experiments were performed in thoracic or abdominal aorta rings with or without endothelium in the presence and absence of NG-nitro-L-arginine methyl ester (L-NAME) (10-5 M), losartan (10-7 M), or PD123319 (10-7 M). AT1 and AT2 receptor expressions were detected by immunohistochemistry. Insulin-induced vasodilation was endothelium- and nitric oxide-dependent and decreased in the thoracic aorta but increased in the abdominal segment of pregnant rats. The insulin's vasorelaxant effect was increased by losartan mainly on the thoracic aorta. PD123319 decreased insulin-induced vasorelaxation mainly in the pregnant rat abdominal aorta. AT1 receptor expression was decreased while AT2 receptor expression was increased by pregnancy. In conclusion, pregnancy changes insulin-induced vasorelaxation. Moreover, insulin vasodilation is tonically inhibited by AT1 receptors, while AT2 receptors appear to have an insulin-sensitizing effect. The role of pregnancy and Ang II receptors differ depending on the aorta segment. These results shed light on the role of pregnancy and Ang II receptors on the regulation of insulin-mediated vasodilation.
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Affiliation(s)
- Betzabel Rodríguez-Reyes
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, México.,Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, México
| | - Cecilia Tufiño
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, México.,Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, México
| | - Ruth M López Mayorga
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, México.,Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, México
| | - Elvia Mera Jiménez
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, México.,Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, México
| | - Rosa Amalia Bobadilla Lugo
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, México.,Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, México
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27
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Liu PJ, Liu Y, Ma L, Liu L, Hu T, An Z, Yao AM, Xia LY. The relationship between plasma taurine levels in early pregnancy and later gestational diabetes mellitus risk in Chinese pregnant women. Sci Rep 2021; 11:7993. [PMID: 33846497 PMCID: PMC8041762 DOI: 10.1038/s41598-021-87178-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 03/23/2021] [Indexed: 11/30/2022] Open
Abstract
Taurine is a sulfur-containing amino acid that plays an important role in glucose homeostasis. However, it remains unknown whether the plasma concentration of taurine affects the risk of later gestational diabetes mellitus (GDM) development. We recruited 398 singleton-pregnancy women and followed up them during the course of pregnancy. We measured the plasma concentrations of taurine based on blood samples collected at nine-week gestation on average and obtained the data regarding both mothers and their infants from medical records. There was a significant increment in the mean value of HOMA-β across the tertiles of plasma taurine in multiparous women rather than in primiparous women. After adjustment for confounders, an increase of plasma taurine was nominally and significantly associated with a decrease risk of GDM; moreover, women with plasma taurine concentrations in the lowest tertile and in the second tertile had a higher risk of GDM than did those with plasma taurine in the top tertile in multiparous women other than primiparous women. Plasma taurine level seems to be associated with insulin secretion in early pregnancy and be more closely associated with β-cell function and the risk of GDM development in multiparas in comparison to primiparas.
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Affiliation(s)
- Peng Ju Liu
- Department of Clinical Nutrition, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, 100730, People's Republic of China
| | - Yanping Liu
- Department of Clinical Nutrition, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, 100730, People's Republic of China.
| | - Liangkun Ma
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, 100730, People's Republic of China.
| | - Lihong Liu
- Pharmacy Department of Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China
| | - Ting Hu
- Pharmacy Department of Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China
| | - Zhuoling An
- Pharmacy Department of Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China
| | - Ai Min Yao
- Department of Gynaecology and Obstetrics, Shunyi Women's and Children's Hospital, Beijing, People's Republic of China
| | - Liang Yu Xia
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, 100730, People's Republic of China
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28
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Schiattarella A, Lombardo M, Morlando M, Rizzo G. The Impact of a Plant-Based Diet on Gestational Diabetes: A Review. Antioxidants (Basel) 2021; 10:antiox10040557. [PMID: 33918528 PMCID: PMC8065523 DOI: 10.3390/antiox10040557] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 03/30/2021] [Accepted: 03/31/2021] [Indexed: 12/13/2022] Open
Abstract
Gestational diabetes mellitus (GDM) represents a challenging pregnancy complication in which women present a state of glucose intolerance. GDM has been associated with various obstetric complications, such as polyhydramnios, preterm delivery, and increased cesarean delivery rate. Moreover, the fetus could suffer from congenital malformation, macrosomia, neonatal respiratory distress syndrome, and intrauterine death. It has been speculated that inflammatory markers such as tumor necrosis factor-alpha (TNF-α), interleukin (IL) 6, and C-reactive protein (CRP) impact on endothelium dysfunction and insulin resistance and contribute to the pathogenesis of GDM. Nutritional patterns enriched with plant-derived foods, such as a low glycemic or Mediterranean diet, might favorably impact on the incidence of GDM. A high intake of vegetables, fibers, and fruits seems to decrease inflammation by enhancing antioxidant compounds. This aspect contributes to improving insulin efficacy and metabolic control and could provide maternal and neonatal health benefits. Our review aims to deepen the understanding of the impact of a plant-based diet on oxidative stress in GDM.
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Affiliation(s)
- Antonio Schiattarella
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (A.S.); (M.M.)
| | - Mauro Lombardo
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy;
| | - Maddalena Morlando
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (A.S.); (M.M.)
| | - Gianluca Rizzo
- Independent Researcher, Via Venezuela 66, 98121 Messina, Italy
- Correspondence: ; Tel.: +39-320-897-6687
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29
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Wang H, Huang B, Hou A, Xue L, Wang B, Chen J, Li M, Zhang JV. High NOV/CCN3 expression during high-fat diet pregnancy in mice affects GLUT3 expression and the mTOR pathway. Am J Physiol Endocrinol Metab 2021; 320:E786-E796. [PMID: 33586490 DOI: 10.1152/ajpendo.00230.2020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
We investigated the expression levels of nephroblastoma overexpressed [NOV or CCN3 (cellular communication network factor 3)] in the serum and placenta of pregnant women and of pregnant mice fed a high-fat diet (HFD), and its effect on placental glucose transporter 3 (GLUT3) expression, to examine its role in gestational diabetes mellitus (GDM). NOV/CCN3 expression was increased in the mouse serum during pregnancy. At gestational day 18, NOV/CCN3 protein expression was increased in the serum and placenta of the HFD mice compared with that of mice fed a normal diet. Compared with non-GDM patients, the patients with GDM had significantly increased serum NOV/CCN3 protein expression and placental NOV/CCN3 mRNA expression. Therefore, we hypothesized that NOV/CCN3 signaling may be involved in the pathogenesis of GDM. We administered NOV/CCN3 recombinant protein via intraperitoneal injections to pregnant mice fed HFD or normal diet. NOV/CCN3 overexpression led to glucose intolerance. Combined with the HFD, NOV/CCN3 exacerbated glucose intolerance and caused insulin resistance. NOV/CCN3 upregulates GLUT3 expression and affects the mammalian target of rapamycin (mTOR) pathway in the GDM environment in vivo and in vitro. In summary, our results demonstrate, for the first time, the molecular mechanism of NOV/CCN3 signaling in maternal metabolism to regulate glucose balance during pregnancy. NOV/CCN3 may be a potential target for detecting and treating GDM.NEW & NOTEWORTHY NOV/CCN3 regulates glucose homeostasis in mice during pregnancy. NOV/CCN3 upregulates GLUT3 expression and affects the mTOR pathway in the GDM environment in vivo and in vitro.
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Affiliation(s)
- Hefei Wang
- Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China
- Department of Clinical Pharmacy and Translational Medicine, School of Pharmacy and Biomedicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China
| | - Binbin Huang
- Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China
- Department of Clinical Pharmacy and Translational Medicine, School of Pharmacy and Biomedicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China
| | - Anli Hou
- Department of Gynaecology, University of Chinese Academy of Sciences Shenzhen Hospital, Shenzhen, People's Republic of China
- Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, People's Republic of China
| | - Li Xue
- Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China
- Department of Clinical Pharmacy and Translational Medicine, School of Pharmacy and Biomedicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China
| | - Baobei Wang
- Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China
- Department of Clinical Pharmacy and Translational Medicine, School of Pharmacy and Biomedicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China
| | - Jie Chen
- Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China
- Department of Clinical Pharmacy and Translational Medicine, School of Pharmacy and Biomedicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China
| | - Mengxia Li
- Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China
- Department of Clinical Pharmacy and Translational Medicine, School of Pharmacy and Biomedicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China
| | - Jian V Zhang
- Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China
- Department of Clinical Pharmacy and Translational Medicine, School of Pharmacy and Biomedicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China
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30
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Ladyman SR, Brooks VL. Central actions of insulin during pregnancy and lactation. J Neuroendocrinol 2021; 33:e12946. [PMID: 33710714 PMCID: PMC9198112 DOI: 10.1111/jne.12946] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 01/24/2021] [Accepted: 01/27/2021] [Indexed: 12/17/2022]
Abstract
Pregnancy and lactation are highly metabolically demanding states. Maternal glucose is a key fuel source for the growth and development of the fetus, as well as for the production of milk during lactation. Hence, the maternal body undergoes major adaptations in the systems regulating glucose homeostasis to cope with the increased demand for glucose. As part of these changes, insulin levels are elevated during pregnancy and lower in lactation. The increased insulin secretion during pregnancy plays a vital role in the periphery; however, the potential effects of increased insulin action in the brain have not been widely investigated. In this review, we consider the impact of pregnancy on brain access and brain levels of insulin. Moreover, we explore the hypothesis that pregnancy is associated with site-specific central insulin resistance that is adaptive, allowing for the increases in peripheral insulin secretion without the consequences of increased central and peripheral insulin functions, such as to stimulate glucose uptake into maternal tissues or to inhibit food intake. Conversely, the loss of central insulin actions may impair other functions, such as insulin control of the autonomic nervous system. The potential role of low insulin in facilitating adaptive responses to lactation, such as hyperphagia and suppression of reproductive function, are also discussed. We end the review with a list of key research questions requiring resolution.
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Affiliation(s)
- Sharon R Ladyman
- Centre for Neuroendocrinology and Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
- Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand
| | - Virginia L Brooks
- Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR, USA
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Nair S, Ormazabal V, Lappas M, McIntyre HD, Salomon C. Extracellular vesicles and their potential role inducing changes in maternal insulin sensitivity during gestational diabetes mellitus. Am J Reprod Immunol 2021; 85:e13361. [PMID: 33064367 DOI: 10.1111/aji.13361] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Revised: 09/11/2020] [Accepted: 09/30/2020] [Indexed: 12/18/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is one of the most common endocrine disorders during gestation and affects around 15% of all pregnancies worldwide, paralleling the global increase in obesity and type 2 diabetes. Normal pregnancies are critically dependent on the development of maternal insulin resistance balanced by an increased capacity to secrete insulin, which allows for the allocation of nutrients for adequate foetal growth and development. Several factors including placental hormones, inflammatory mediators and nutrients have been proposed to alter insulin sensitivity and insulin response and underpin the pathological outcomes of GDM. However, other factors may also be involved in the regulation of maternal metabolism and a complete understanding of GDM pathophysiology requires the identification of these factors, and the mechanisms associated with them. Recent studies highlight the potential utility of tissue-specific extracellular vesicles (EVs) in the diagnosis of disease onset and treatment monitoring for several pregnancy-related complications, including GDM. To date, there is a paucity of data defining changes in the release, content, bioactivity and diagnostic utility of circulating EVs in pregnancies complicated by GDM. Placental EVs may engage in paracellular interactions including local cell-to-cell communication between the cell constituents of the placenta and contiguous maternal tissues, and/or distal interactions involving the release of placental EVs into biological fluids and their transport to a remote site of action. Hence, the aim of this review is to discuss the biogenesis, isolation methods and role of EVs in the physiopathology of GDM, including changes in maternal insulin sensitivity during pregnancy.
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Affiliation(s)
- Soumyalekshmi Nair
- Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, QLD, Australia
| | - Valeska Ormazabal
- Department of Pharmacology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile
| | - Martha Lappas
- Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Vic., Australia.,Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Vic., Australia
| | - H David McIntyre
- Mater Research, The University of Queensland, South Brisbane, Qld, Australia
| | - Carlos Salomon
- Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, QLD, Australia.,Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile
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Dearden L, Bouret SG, Ozanne SE. Nutritional and developmental programming effects of insulin. J Neuroendocrinol 2021; 33:e12933. [PMID: 33438814 DOI: 10.1111/jne.12933] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 11/24/2020] [Accepted: 12/11/2020] [Indexed: 02/06/2023]
Abstract
The discovery of insulin in 1921 was a major breakthrough in medicine and for therapy in patients with diabetes. The dramatic rise in the prevalence of overweight and obesity has been tightly linked to an increased prevalence of gestational diabetes mellitus (GDM), which poses major health concerns. Babies born to GDM mothers are more likely to develop obesity, type 2 diabetes and cardiovascular disease later in life. Evidence accumulated during the past two decades has revealed that high levels insulin, such as those observed during GDM, can have a widespread effect on the development and function of a variety of organs. This review summarises our current knowledge on the role of insulin in the placenta, cardiovascular system and brain during critical periods of development, as well as how it can contribute to lifelong metabolic regulation. We also discuss possible intervention strategies to ameliorate and hopefully reverse the developmental defects associated with obesity and GDM.
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Affiliation(s)
- Laura Dearden
- MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories, Cambridge, UK
| | - Sebastien G Bouret
- Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition Research Center, Lille, France
- University of Lille, Lille, France
| | - Susan E Ozanne
- MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories, Cambridge, UK
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CTRP-1 levels are related to insulin resistance in pregnancy and gestational diabetes mellitus. Sci Rep 2020; 10:17345. [PMID: 33060724 PMCID: PMC7562865 DOI: 10.1038/s41598-020-74413-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 09/28/2020] [Indexed: 01/13/2023] Open
Abstract
Recent studies have shown higher levels of CTRP-1 (C1QTNF-related protein) in patients with type 2 diabetes compared to controls. We aimed at investigating CTRP-1 in gestational diabetes mellitus (GDM). CTRP-1 levels were investigated in 167 women (93 with normal glucose tolerance (NGT), 74 GDM) of a high-risk population for GDM. GDM was further divided into GDM subtypes depending on a predominant insulin sensitivity issue (GDM-IR) or secretion deficit (GDM-IS). Glucose tolerance was assessed with indices [Matsuda index, Stumvoll first phase index, insulin-secretion-sensitivity-index 2 (ISSI-2), area-under-the-curve (AUC) insulin, AUC glucose] derived from an oral glucose tolerance test (oGTT) performed at < 21 and 24–28 weeks of gestation. In pregnancy, CTRP-1 levels of GDM (76.86 ± 37.81 ng/ml) and NGT (82.2 ± 35.34 ng/ml; p = 0.104) were similar. However, GDM-IR women (65.18 ± 42.18 ng/ml) had significantly lower CTRP-1 levels compared to GDM-IS (85.10 ± 28.14 ng/ml; p = 0.009) and NGT (p = 0.006). CTRP-1 levels correlated negatively with weight, AUC insulin, Stumvoll first phase index, bioavailable estradiol and positively with HbA1c, Matsuda Index and ISSI-2. A multiple regression analysis revealed bioavailable estradiol (β = − 0.280, p = 0.008) and HbA1c (β = 0.238; p = 0.018) as the main variables associated with CTRP-1 in GDM. Postpartum, waist and hip measurements were predictive of CRTP-1 levels instead. CTRP-1 levels were higher postpartum than during pregnancy (91.92 ± 47.27 vs.82.44 ± 38.99 ng/ml; p = 0.013). CTRP-1 is related to insulin resistance in pregnancy and might be a metabolic biomarker for insulin resistance in GDM. CTRP-1 levels were significantly lower during pregnancy than postpartum, probably due to rising insulin resistance during pregnancy.
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Tozour J, Hughes F, Carrier A, Vieau D, Delahaye F. Prenatal Hyperglycemia Exposure and Cellular Stress, a Sugar-Coated View of Early Programming of Metabolic Diseases. Biomolecules 2020; 10:E1359. [PMID: 32977673 PMCID: PMC7598660 DOI: 10.3390/biom10101359] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 09/15/2020] [Accepted: 09/16/2020] [Indexed: 12/21/2022] Open
Abstract
Worldwide, the number of people with diabetes has quadrupled since 1980 reaching 422 million in 2014 (World Health Organization). This distressing rise in diabetes also affects pregnant women and thus, in regard to early programming of adult diseases, creates a vicious cycle of metabolic dysfunction passed from one generation to another. Metabolic diseases are complex and caused by the interplay between genetic and environmental factors. High-glucose exposure during in utero development, as observed with gestational diabetes mellitus (GDM), is an established risk factor for metabolic diseases. Despite intense efforts to better understand this phenomenon of early memory little is known about the molecular mechanisms associating early exposure to long-term diseases risk. However, evidence promotes glucose associated oxidative stress as one of the molecular mechanisms able to influence susceptibility to metabolic diseases. Thus, we decided here to further explore the relationship between early glucose exposure and cellular stress in the context of early development, and focus on the concept of glycemic memory, its consequences, and sexual dimorphic and epigenetic aspects.
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Affiliation(s)
- Jessica Tozour
- Department of Obstetrics and Gynecology, NYU Winthrop Hospital, Mineola, NY 11501, USA;
| | - Francine Hughes
- Obstetrics & Gynecology and Women’s Health, Division of Maternal-Fetal Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY 10461, USA;
| | - Arnaud Carrier
- Institut Pasteur de Lille, U1283-UMR 8199 EGID, Université de Lille, Inserm, CNRS, CHU Lille, F-59000 Lille, France;
| | - Didier Vieau
- BiologyDepartment, LilNCog Lille Neurosciences and Cognition U 1172, Université de Lille, Inserm, CHU Lille, F-59000 Lille, France;
| | - Fabien Delahaye
- Institut Pasteur de Lille, U1283-UMR 8199 EGID, Université de Lille, Inserm, CNRS, CHU Lille, F-59000 Lille, France;
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Sartorão Filho CI, Pinheiro FA, Prudencio CB, Nunes SK, Takano L, Enriquez EMA, Orlandi MIG, Junginger B, Hallur RLS, Rudge MVC, Barbosa AMP. Impact of gestational diabetes on pelvic floor: A prospective cohort study with three-dimensional ultrasound during two-time points in pregnancy. Neurourol Urodyn 2020; 39:2329-2337. [PMID: 32857893 DOI: 10.1002/nau.24491] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 08/10/2020] [Indexed: 01/24/2023]
Abstract
AIM To evaluate the pelvic floor (PF) biometry using three-dimensional ultrasound (US) at two-time points of gestational in pregnant women with gestational diabetes mellitus (GDM). METHODS A prospective cohort study conducted at the Perinatal Diabetes Research Center including 44 pregnant women with GDM and 66 pregnant women without GDM at 24 to 28 weeks of gestation. Three-dimensional transperineal US was performed at 24 to 28 and 34 to 38 weeks of gestation in the lithotomy position at rest. The axial plane of the minimal Levator hiatal dimensions was used to determine Levator ani muscle and Hiatal area (HA) biometry at 24 to 28 and 34 to 38 weeks of gestation. RESULTS Of the 110 pregnant women, 100 (90.9%) completed the follow-up at 34 to 38 weeks of gestation. The evaluation by US showed a negative biometric change between the two-time points, during pregnancy in women with GDM; in the HA (β coefficient: estimative of effect in biometric progression according to GDM diagnosis, using the non-GDM group as reference = -6.76; P = .020), anteroposterior diameter (β = -5.07; P = .019), and Levator ani thickness (β = -12.34; P = .005). CONCLUSIONS Pregnant women with GDM had a significantly lower than expected percentage of changes in biometry of Levator ani thickness and HA from 24 to 28 to 34 to 38 weeks of gestation when compared with the group of pregnant women without GDM. GDM alters the morphology of PF structures assessed by three-dimension US. This reported complication may be implicated in adverse birth outcomes and may play a role in the development of PF dysfunction.
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Affiliation(s)
- Carlos I Sartorão Filho
- Department of Gynecology and Obstetrics, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.,Department of Medicine, Assis Municipality Educational Foundation (FEMA), Medical School, Fundação Educacional do Município de Assis (FEMA), Assis, São Paulo, Brazil
| | - Fabiane A Pinheiro
- Department of Gynecology and Obstetrics, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Caroline B Prudencio
- Department of Gynecology and Obstetrics, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Sthefanie K Nunes
- Department of Gynecology and Obstetrics, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Luiz Takano
- Department of Gynecology and Obstetrics, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Eusebio M A Enriquez
- Department of Gynecology and Obstetrics, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Maiara I G Orlandi
- Department of Gynecology and Obstetrics, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Baerbel Junginger
- Department of Gynecology, Pelvic Floor Center Charité, Charité University Hospital, Berlin, Germany
| | - Raghavendra L S Hallur
- Department of Gynecology and Obstetrics, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Marilza V C Rudge
- Department of Gynecology and Obstetrics, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Angélica M P Barbosa
- Department of Gynecology and Obstetrics, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.,Department of Physiotherapy and Occupational Therapy, School of Philosophy and Sciences, São Paulo State University (UNESP), Marilia, São Paulo, Brazil
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Nguyen-Ngo C, Willcox JC, Lappas M. Anti-inflammatory effects of phenolic acids punicalagin and curcumin in human placenta and adipose tissue. Placenta 2020; 100:1-12. [PMID: 32814232 DOI: 10.1016/j.placenta.2020.08.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 07/31/2020] [Accepted: 08/03/2020] [Indexed: 01/04/2023]
Abstract
INTRODUCTION The world is witnessing a steady rise in the prevalence of gestational diabetes mellitus (GDM), correlated with the current obesity epidemic. Both GDM and obesity negatively impact both the health of women but also that of the next generation. GDM and maternal obesity are associated with increased maternal and fetal inflammation and oxidative stress. A safe and effective intervention that can prevent these pathological features, and reduce the intergenerational burden, is required. Phenolic acids, such as punicalagin and curcumin, possess anti-inflammatory and antioxidant properties. Thus, the aim of this study was to examine the effects of punicalagin and curcumin on pro-inflammatory cytokines and chemokines, and antioxidant expression in an in vitro model of inflammation. METHODS Human placenta, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) explants were obtained at term elective Caesarean section and stimulated with TNF alpha (TNF). RESULTS We found that punicalagin and curcumin significantly supressed TNF-induced pro-inflammatory cytokine (IL1A, IL1B, and IL6) and chemokine (CCL2-4, CXCL1, CXCL5 and CXCL8) expression in human placenta, VAT and SAT. Anti-inflammatory cytokine IL4 and IL13 mRNA expression was also upregulated by punicalagin and curcumin treatment in placenta, VAT and SAT. Punicalagin and curcumin also altered antioxidant (SOD2 and catalase) mRNA expression in placenta, VAT and SAT, with minimal effect on hydrogen peroxide concentrations in tissue lysates. CONCLUSION These findings suggest that the phenolic acids punicalagin and curcumin possess potent anti-inflammatory capabilities in in vitro human models of inflammation. Further studies are warranted to determine their suitability as therapeutic interventions for pro-inflammatory gestational complications, including GDM and maternal obesity.
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Affiliation(s)
- Caitlyn Nguyen-Ngo
- Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Victoria, Australia; Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia
| | - Jane C Willcox
- Dietetics and Human Nutrition, School of Allied Health, Human Services and Sport, La Trobe University, Bundoora, Victoria, Australia
| | - Martha Lappas
- Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Victoria, Australia; Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
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Nair S, Salomon C. Extracellular vesicles as critical mediators of maternal-fetal communication during pregnancy and their potential role in maternal metabolism. Placenta 2020; 98:60-68. [PMID: 33039033 DOI: 10.1016/j.placenta.2020.06.011] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 06/12/2020] [Accepted: 06/15/2020] [Indexed: 01/06/2023]
Abstract
Extracellular vesicles (EVs) have been implicated in the pathophysiology of metabolic disorders by transferring biologically active molecules such as miRNAs and proteins to recipient cells, and influencing their metabolic pathways. Pregnancy is one of the greatest metabolic challenges faced by both the mother and the growing fetus, and this is fine-tuned by several factors, including hormones, soluble molecules, and molecules encapsulated in EVs released from the placenta. A wide range of EVs originating from the placenta are present in maternal circulation, and changes in their circulating levels and bioactivity (i.e., capacity to induce changes in the target cells) have been associated with several complications of pregnancies, including gestational diabetes mellitus (GDM), preeclampsia, preterm birth, and fetal growth restriction. Complications of pregnancies are associated with maternal metabolic dysfunction with short- and long-term consequences for both mother and child. However, the potential roles of circulating EVs originating from the placenta and other tissues (e.g. adipose tissue), on changes in maternal metabolism during normal and pregnancy complications have not been fully described. The aim of this brief review, thus, is to discuss the diversity of EVs, and their potential roles in the metabolic alterations during pregnancy, with a special focus on GDM.
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Affiliation(s)
- Soumyalekshmi Nair
- Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, QLD, 4029, Australia
| | - Carlos Salomon
- Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, QLD, 4029, Australia; Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile.
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Campodonico-Burnett W, Hetrick B, Wesolowski SR, Schenk S, Takahashi DL, Dean TA, Sullivan EL, Kievit P, Gannon M, Aagaard K, Friedman JE, McCurdy CE. Maternal Obesity and Western-Style Diet Impair Fetal and Juvenile Offspring Skeletal Muscle Insulin-Stimulated Glucose Transport in Nonhuman Primates. Diabetes 2020; 69:1389-1400. [PMID: 32354857 PMCID: PMC7306120 DOI: 10.2337/db19-1218] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Accepted: 04/28/2020] [Indexed: 12/12/2022]
Abstract
Infants born to mothers with obesity have a greater risk for childhood obesity and metabolic diseases; however, the underlying biological mechanisms remain poorly understood. We used a Japanese macaque model to investigate whether maternal obesity combined with a Western-style diet (WSD) impairs offspring muscle insulin action. Adult females were fed a control or WSD prior to and during pregnancy through lactation, and offspring subsequently weaned to a control or WSD. Muscle glucose uptake and signaling were measured ex vivo in fetal (n = 5-8/group) and juvenile (n = 8/group) offspring. In vivo signaling was evaluated after an insulin bolus just prior to weaning (n = 4-5/group). Maternal WSD reduced insulin-stimulated glucose uptake and impaired insulin signaling at the level of Akt phosphorylation in fetal muscle. In juvenile offspring, insulin-stimulated glucose uptake was similarly reduced by both maternal and postweaning WSD and corresponded to modest reductions in insulin-stimulated Akt phosphorylation relative to controls. We conclude that maternal WSD leads to a persistent decrease in offspring muscle insulin-stimulated glucose uptake even in the absence of increased offspring adiposity or markers of systemic insulin resistance. Switching offspring to a healthy diet did not reverse the effects of maternal WSD on muscle insulin action, suggesting earlier interventions may be warranted.
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Affiliation(s)
- William Campodonico-Burnett
- Department of Human Physiology, University of Oregon, Eugene, OR
- Department of Biochemistry, University of Colorado Boulder, Boulder, CO
| | - Byron Hetrick
- Department of Human Physiology, University of Oregon, Eugene, OR
| | | | - Simon Schenk
- Department of Orthopaedic Surgery, University of California, San Diego, La Jolla, CA
- Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA
| | - Diana L Takahashi
- Division of Cardiometabolic Health, Oregon National Primate Research Center, Oregon Health Science University, Beaverton, OR
| | - Tyler A Dean
- Division of Cardiometabolic Health, Oregon National Primate Research Center, Oregon Health Science University, Beaverton, OR
| | - Elinor L Sullivan
- Department of Human Physiology, University of Oregon, Eugene, OR
- Division of Neuroscience, Oregon National Primate Research Center, Oregon Health Science University, Beaverton, OR
- Department of Psychiatry, Oregon Health Science University, Portland, OR
- Department of Behavioral Sciences, Oregon Health Science University, Portland, OR
| | - Paul Kievit
- Division of Cardiometabolic Health, Oregon National Primate Research Center, Oregon Health Science University, Beaverton, OR
| | - Maureen Gannon
- Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Kjersti Aagaard
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX
| | - Jacob E Friedman
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK
| | - Carrie E McCurdy
- Department of Human Physiology, University of Oregon, Eugene, OR
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Roland MCP, Lekva T, Godang K, Bollerslev J, Henriksen T. Changes in maternal blood glucose and lipid concentrations during pregnancy differ by maternal body mass index and are related to birthweight: A prospective, longitudinal study of healthy pregnancies. PLoS One 2020; 15:e0232749. [PMID: 32574162 PMCID: PMC7310681 DOI: 10.1371/journal.pone.0232749] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Accepted: 04/21/2020] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Maternal obesity is increasing worldwide but the consequences for maternal physiology and fetal growth are not fully understood. OBJECTIVE To study whether changes in glucose and lipid metabolism during pregnancy differ between women with normal weight and overweight/obesity, and investigate which of these metabolic factors are associated with birthweight. DESIGN Prospective, longitudinal study. SETTING Department of Obstetrics, Oslo University Hospital, Rikshospitalet. POPULATION 1031 healthy pregnant women with singleton pregnancies. METHODS Blood samples from early and late pregnancy were analyzed for fasting glucose, insulin and lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Associations between metabolic factors and birthweight (z-scores) were explored by linear regression models. Main Outcome Measures: Group-dependent longitudinal changes in glucose and lipids and their association with birthweight (z-scores). RESULTS Compared to women with normal weight (BMI < 25), women with overweight (BMI 25-29.9) and obesity (BMI > 30) had significantly higher fasting glucose (4.54, 4.68 and 4.84 mmol/l), insulin (23, 33 and 50 pmol/l), total cholesterol (4.85, 4.99 and 5.14 mmol/l), LDL-C (2.49, 2.66 and 2.88 mmol/l) and triglycerides (1.10, 1.28 and 1.57 mmol/l), but lower HDL-C (1.86, 1.75 and 1.55 mmol/l). BMI (B 0.05, 95% CI 0.03-0.06, p<0.001), gestational weight gain (GWG) (B 0.06, 0.05-0.08, p<0.001) and an increase in fasting glucose (B 0.30, 0.16-0.43, p<0.001) were positively associated with birthweight, whereas a decrease in HDL-C (B -0.72, -0.96- -0.53, p<0.001) had a negative association with birthweight. CONCLUSIONS Overweight/obesity was associated with an unfavorable metabolic profile in early pregnancy which was associated with increased birthweight. However, modifiable factors like gestational weight gain and an increase in fasting glucose were identified and can be targeted for interventions.
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Affiliation(s)
- Marie Cecilie Paasche Roland
- Department of Obstetrics, Oslo University Hospital, Oslo, Norway
- National Advisory Unit on Women’s Health, Oslo University Hospital, Oslo, Norway
- * E-mail:
| | - Tove Lekva
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
| | - Kristin Godang
- Department of Endocrinology, Oslo University Hospital, Oslo, Norway
| | - Jens Bollerslev
- Department of Endocrinology, Oslo University Hospital, Oslo, Norway
- Department of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Tore Henriksen
- Department of Clinical Medicine, University of Oslo, Oslo, Norway
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Khan MW, Layden BT. Gestational Glucose Metabolism: Focus on the Role and Mechanisms of Insulin Resistance. MATERNAL-FETAL AND NEONATAL ENDOCRINOLOGY 2020:75-90. [DOI: 10.1016/b978-0-12-814823-5.00006-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Naringenin improves insulin sensitivity in gestational diabetes mellitus mice through AMPK. Nutr Diabetes 2019; 9:28. [PMID: 31591391 PMCID: PMC6779739 DOI: 10.1038/s41387-019-0095-8] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 06/20/2019] [Accepted: 07/25/2019] [Indexed: 01/13/2023] Open
Abstract
Background Gestational diabetes mellitus (GDM) is a temporary form of diabetes during pregnancy, which influences the health of maternal-child in clinical practice. It is still urgent to develop new effective treatment for GDM. Naringenin is a bioactive ingredient with multiple activities including anti-diabetic. In current study, the effects of naringenin on GDM symptoms, insulin tolerance, inflammation, and productive outcomes were evaluated and the underlying mechanisms were explored. Methods We administrated naringenin to GDM mice and monitored the GDM symptoms, glucose and insulin tolerance, inflammation and productive outcomes. We established tumor necrosis factor alpha (TNF-α)-induced insulin resistance skeletal muscle cell model and evaluated the effects of naringenin on reactive oxygen species (ROS) production, glucose uptake and glucose transporter type 4 (GLUT4) membrane translocation. Results We found that naringenin ameliorated GDM symptoms, improved glucose and insulin tolerance, inhibited inflammation, and improved productive outcomes. It was further found that naringenin inhibited TNF-α-induced ROS production, enhanced GLUT4 membrane translocation, and glucose uptake, which were abolished by inhibition of AMP-activated protein kinase (AMPK). Conclusion Naringenin improves insulin sensitivity in gestational diabetes mellitus mice in an AMPK-dependent manner.
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Steyn A, Crowther NJ, Norris SA, Rabionet R, Estivill X, Ramsay M. Epigenetic modification of the pentose phosphate pathway and the IGF-axis in women with gestational diabetes mellitus. Epigenomics 2019; 11:1371-1385. [PMID: 31583916 DOI: 10.2217/epi-2018-0206] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: Gestational diabetes mellitus (GDM) has been linked with adverse long-term health outcomes for the fetus and mother. These effects may be mediated by epigenetic modifications. Materials & methods: Genome-wide RNA sequencing was performed in placental tissue and maternal blood in six GDM and six non-GDM pregnancies. Promoter region DNA methylation was examined for selected genes and correlated with gene expression to examine an epigenetic modulator mechanism. Results: Reductions of mRNA expression and increases in promoter methylation were observed for G6PD in GDM women, and for genes encoding IGF-binding proteins in GDM-exposed placenta. Conclusion: GDM involves epigenetic attenuation of G6PD, which may lead to hyperglycemia and oxidative stress, and the IGF-axis, which may modulate fetal macrosomia.
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Affiliation(s)
- Angela Steyn
- Division of Human Genetics, National Health Laboratory Service and the School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa
| | - Nigel J Crowther
- Division of Human Genetics, National Health Laboratory Service and the School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa.,The Department of Chemical Pathology, School of Pathology, University of the Witwatersrand, Johannesburg, Gauteng, South Africa
| | - Shane A Norris
- Developmental Pathways for Health Research Unit, University of the Witwatersrand, Johannesburg, Gauteng, South Africa
| | - Raquel Rabionet
- The Centre for Genomic Regulation, Genes and Diseases Program, Barcelona, Spain
| | - Xavier Estivill
- The Centre for Genomic Regulation, Genes and Diseases Program, Barcelona, Spain
| | - Michèle Ramsay
- Division of Human Genetics, National Health Laboratory Service and the School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa.,The Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa
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Lu M, Ma L, Shan P, Liu A, Yu X, Jiang W, Wang X, Zhao X, Ye X, Wang T. DYRK1A aggravates β cell dysfunction and apoptosis by promoting the phosphorylation and degradation of IRS2. Exp Gerontol 2019; 125:110659. [PMID: 31306739 DOI: 10.1016/j.exger.2019.110659] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 07/12/2019] [Accepted: 07/12/2019] [Indexed: 01/21/2023]
Abstract
In this study, we aimed to investigate the role of dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A), which is one of the most important regulators of Alzheimer's disease development, in islet β cell dysfunction and apoptosis. We found significantly increased expression of DYRK1A in both the hippocampus and pancreatic islets of APPswe/PS1ΔE9 transgenic mice than in wild-type littermates. Furthermore, we observed that the overexpression of DYRK1A greatly aggravated β cell apoptosis. Most importantly, we found that DYRK1A directly interacted with insulin receptor substrate-2 (IRS2) and promoted IRS2 phosphorylation, leading to the proteasomal degradation of IRS2 and promotion of β cell dysfunction and apoptosis. These findings suggested that DYRK1A is a potential drug target in diabetes mellitus.
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Affiliation(s)
- Mei Lu
- Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China; Shandong Provincial Key laboratory of Cardiovascular Proteomics, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Lin Ma
- Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China; Shandong Provincial Key laboratory of Cardiovascular Proteomics, Qilu Hospital of Shandong University, Jinan, Shandong, China.
| | - Peiyan Shan
- Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China; Shandong Provincial Key laboratory of Cardiovascular Proteomics, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Aifen Liu
- Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Xiaolin Yu
- Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Wenjing Jiang
- Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Xinbang Wang
- Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Xinjing Zhao
- Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Xiang Ye
- Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Tan Wang
- Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China
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Mohammed A, Aliyu IS, Manu M. Correlation between circulating level of tumor necrosis factor-alpha and insulin resistance in Nigerian women with gestational diabetes mellitus. Ann Afr Med 2019; 17:168-171. [PMID: 30588928 PMCID: PMC6330778 DOI: 10.4103/aam.aam_53_16] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Background: Gestational diabetes mellitus (GDM) results from an imbalance between insulin resistance and insulin secretion capacity during pregnancy. Tumor necrosis factor-alpha (TNF-α) is an inflammatory cytokine that is proposed to be involved in the pathogenesis of the insulin resistance, but the findings from studies across different ethnic groups are inconsistent or even conflicting. Aim: The aim of this study is to determine the relationship between maternal circulating level of TNF-α and insulin resistance in pregnant Nigerian women with GDM. Methodology: This was a cross-sectional analytical study involving 100 women with GDM and another 100 pregnant women with normal gestation. They were evaluated between 24 and 28 weeks’ gestation. Diagnosis of GDM was based on the WHO diagnostic criteria. Fasting serum insulin and TNF-α levels were measured. Insulin resistance index was calculated as homeostasis model assessment of insulin resistance. Multivariate correlation analysis was used to determine the relationship between the maternal serum level of TNF-α and the insulin resistance. Results: Pregnant women with GDM had greater insulin resistance than observed in the normal controls (3.14 ± 0.19 vs. 2.89 ± 0.20, P < 0.05). There was a positive correlation between serum TNF-α level and insulin resistance among the pregnant women with GDM (r = 0.49, P < 0.05). Multiple linear regression analysis indicated that TNF-α is a predictor of insulin resistance in pregnancies complicated by GDM. Conclusion: It is concluded that among pregnant Nigerian women with GDM in this study, increased serum TNF-α level is associated with greater insulin resistance independent of age and body mass index.
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Affiliation(s)
- Abdullahi Mohammed
- Department of Chemical Pathology, Federal Teaching Hospital, Gombe, Nigeria
| | | | - Mohammed Manu
- Department of Chemical Pathology, Ahmadu Bello University, Zaria, Nigeria
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Powe CE, Huston Presley LP, Locascio JJ, Catalano PM. Augmented insulin secretory response in early pregnancy. Diabetologia 2019; 62:1445-1452. [PMID: 31177313 PMCID: PMC6786902 DOI: 10.1007/s00125-019-4881-6] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 03/18/2019] [Indexed: 01/15/2023]
Abstract
AIMS/HYPOTHESIS This study aimed to examine changes in the insulin secretory response in early pregnancy, while accounting for changes in insulin sensitivity. METHODS This is a secondary analysis of a previously conducted longitudinal physiological study. In 34 women, insulin secretory response (by IVGTT) and insulin sensitivity (by euglycaemic clamp) were assessed prior to pregnancy, in early pregnancy (12-14 weeks gestation) and in late pregnancy (34-36 weeks gestation). Using mixed-effects models, we compared insulin secretory response and sensitivity in early pregnancy to the same variables prior to pregnancy and in late pregnancy, with adjustment for age, obesity status and gestational diabetes mellitus (GDM). We examined changes in insulin secretory response after adjustment for insulin sensitivity using both multivariate modelling and the disposition index (DI). We explored the relationship between insulin secretory response and circulating hormones. RESULTS The insulin secretory response increased from prior to pregnancy to early pregnancy (unadjusted mean [SD] first-phase insulin response 465.1 [268.5] to 720 [358.2], p < 0.0001) and from early pregnancy to late pregnancy (to 924 [494.6], p = 0.01). Insulin sensitivity increased from prior to pregnancy to early pregnancy (insulin sensitivity index 0.10 [0.04] to 0.12 [0.05], p = 0.001) and decreased in late pregnancy (to 0.06 [0.03], p < 0.0001). Accounting for changes in insulin sensitivity, using either multivariate modelling or the DI, did not attenuate the early-pregnancy augmentation of insulin secretory response. Leptin was positively associated with insulin secretory response, independent of insulin sensitivity and adiposity (p = 0.004). Adjustment for leptin attenuated the observed augmentation of insulin secretory response in early pregnancy (adjusted mean change 121.5, p = 0.13). CONCLUSIONS/INTERPRETATION The insulin secretory response increases markedly in early pregnancy, prior to and independent of changes in insulin sensitivity. Circulating hormones may mediate this metabolic adaptation. Identifying mediators of this physiological effect could have therapeutic implications for treating hyperglycaemia during and outside of pregnancy.
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Affiliation(s)
- Camille E Powe
- Diabetes Unit, Endocrine Division, Massachusetts General Hospital, 50 Staniford Street, Suite 301, Boston, MA, 02114, USA.
- Harvard Medical School, Boston, MA, USA.
| | - Larraine P Huston Presley
- Department of Reproductive Biology, Case Western Reserve University, MetroHealth Medical Center, Cleveland, OH, USA
| | - Joseph J Locascio
- Alzheimer's Disease Research Center, Neurology Dept, Massachusetts General Hospital, Boston, MA, USA
| | - Patrick M Catalano
- Mother Infant Research Institute, Department of Obstetrics and Gynecology, Tufts University School of Medicine, Boston, MA, USA
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
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McIntyre HD, Catalano P, Zhang C, Desoye G, Mathiesen ER, Damm P. Gestational diabetes mellitus. Nat Rev Dis Primers 2019; 5:47. [PMID: 31296866 DOI: 10.1038/s41572-019-0098-8] [Citation(s) in RCA: 959] [Impact Index Per Article: 159.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/29/2019] [Indexed: 12/11/2022]
Abstract
Hyperglycaemia that develops during pregnancy and resolves after birth has been recognized for over 50 years, but uniform worldwide consensus is lacking about threshold hyperglycaemic levels that merit a diagnosis of 'gestational diabetes mellitus' (GDM) and thus treatment during pregnancy. GDM is currently the most common medical complication of pregnancy, and prevalence of undiagnosed hyperglycaemia and even overt diabetes in young women is increasing. Maternal overweight and obesity, later age at childbearing, previous history of GDM, family history of type 2 diabetes mellitus and ethnicity are major GDM risk factors. Diagnosis is usually performed using an oral glucose tolerance test (OGTT), although a non-fasting, glucose challenge test (GCT) is used in some parts of the world to screen women for those requiring a full OGTT. Dietary modification and increased physical activity are the primary treatments for GDM, but pharmacotherapy, usually insulin, is used when normoglycaemia is not achieved. Oral hypoglycaemic agents, principally metformin and glibenclamide (glyburide), are also used in some countries. Treatment improves immediate pregnancy outcomes, reducing excess fetal growth and adiposity and pregnancy-related hypertensive disorders. GDM increases the risk of long-term complications, including obesity, impaired glucose metabolism and cardiovascular disease, in both the mother and infant. Optimal management of mother and infant during long-term follow-up remains challenging, with very limited implementation of preventive strategies in most parts of the world.
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Affiliation(s)
- H David McIntyre
- Mater Research and University of Queensland, Brisbane, Queensland, Australia.
| | - Patrick Catalano
- Mother Infant Research Institute, Department of Obstetrics and Gynecology, Tufts University School of Medicine, Friedman School of Nutrition Science and Policy, Boston, MA, USA
| | - Cuilin Zhang
- Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
| | - Gernot Desoye
- Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria
| | - Elisabeth R Mathiesen
- Department of Endocrinology, Center for Pregnant Women with Diabetes, Rigshospitalet and The Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Peter Damm
- Department of Obstetrics, Center for Pregnant Women with Diabetes, Rigshospitalet and The Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Saande CJ, Steffes MA, Webb JL, Valentine RJ, Rowling MJ, Schalinske KL. Whole Egg Consumption Impairs Insulin Sensitivity in a Rat Model of Obesity and Type 2 Diabetes. Curr Dev Nutr 2019; 3:nzz015. [PMID: 31008440 PMCID: PMC6462456 DOI: 10.1093/cdn/nzz015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 02/20/2019] [Accepted: 03/06/2019] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND The literature regarding the relation between egg consumption and type 2 diabetes (T2D) is inconsistent and there is limited evidence pertaining to the impact of egg consumption on measures of insulin sensitivity. OBJECTIVES The aim of this study was to investigate the effect of dietary whole egg on metabolic biomarkers of insulin resistance in T2D rats. METHODS Male Zucker diabetic fatty (ZDF) rats (n = 12; 6 wk of age) and age-matched lean controls (n = 12) were randomly assigned to be fed a casein- or whole egg-based diet. At week 5 of dietary treatment, an insulin tolerance test (ITT) was performed on all rats and blood glucose was measured by glucometer. After 7 wk of dietary treatment, rats were anesthetized and whole blood was collected via a tail vein bleed. Following sedation, the extensor digitorum longus muscle was removed before and after an intraperitoneal insulin injection, and insulin signaling in skeletal muscle was analyzed by Western blot. Serum glucose and insulin were analyzed by ELISA for calculation of the homeostatic model assessment of insulin resistance (HOMA-IR). RESULTS Mean ITT blood glucose over the course of 60 min was 32% higher in ZDF rats fed the whole egg-based diet than in ZDF rats fed the casein-based diet. Furthermore, whole egg consumption increased fasting blood glucose by 35% in ZDF rats. Insulin-stimulated phosphorylation of key proteins in the insulin signaling pathway did not differ in skeletal muscle of ZDF rats fed casein- and whole egg-based diets. In lean rats, no differences were observed in insulin tolerance, HOMA-IR and skeletal muscle insulin signaling, regardless of experimental dietary treatment. CONCLUSIONS These data suggest that whole body insulin sensitivity may be impaired by whole egg consumption in T2D rats, although no changes were observed in skeletal muscle insulin signaling that could explain this finding.
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Affiliation(s)
- Cassondra J Saande
- Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011
- Interdepartmental Graduate Program in Nutritional Sciences, Iowa State University, Ames, IA 50011
| | - Megan A Steffes
- Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011
| | - Joseph L Webb
- Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011
- Interdepartmental Graduate Program in Nutritional Sciences, Iowa State University, Ames, IA 50011
| | - Rudy J Valentine
- Interdepartmental Graduate Program in Nutritional Sciences, Iowa State University, Ames, IA 50011
- Department of Kinesiology, Iowa State University, Ames, IA, 50011
| | - Matthew J Rowling
- Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011
- Interdepartmental Graduate Program in Nutritional Sciences, Iowa State University, Ames, IA 50011
| | - Kevin L Schalinske
- Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011
- Interdepartmental Graduate Program in Nutritional Sciences, Iowa State University, Ames, IA 50011
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Calan M, Arkan T, Kume T, Bayraktar F. The relationship between urotensin II and insulin resistance in women with gestational diabetes mellitus. Hormones (Athens) 2019; 18:91-97. [PMID: 30471011 DOI: 10.1007/s42000-018-0084-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Accepted: 11/15/2018] [Indexed: 02/07/2023]
Abstract
AIM Urotensin II (UII), a pluripotent vasoactive peptide, plays a crucial role in development of insulin resistance. Gestational diabetes mellitus (GDM) is a metabolic disorder associated with insulin resistance. The aims of the current study were to compare UII levels in women with or without GDM and to investigate the relationship between UII and insulin resistance in women with GDM. METHODS A total of 84 women were recruited in this case-control study (42 women with GDM and 42 age- and body mass index (BMI)-matched pregnant women without GDM as controls). GDM was diagnosed by a 2-h 75-g oral glucose tolerance test over a period of 24-28 gestational weeks. Circulating UII levels were assessed via the ELISA method. The metabolic parameters of the recruited women were also determined. RESULTS The circulating levels of UII in women with GDM were higher than in controls (11.56 ± 4.13 vs. 7.62 ± 3.45 ng/ml, P < 0.001). UII showed a positive correlation with insulin resistance marker (HOMA-IR), fasting blood glucose, and BMI. Moreover, according to the results of multiple linear regression analyses, UII was independently related to HOMA-IR. Additionally, the binary logistic analysis revealed that the women with the highest tertile of UII levels showed increased risk for GDM by comparison with those women with the lowest tertile of UII levels. CONCLUSION Elevated UII levels are associated with insulin resistance in women with GDM.
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Affiliation(s)
- Mehmet Calan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Izmir Bozyaka Training and Research Hospital, Bozyaka, 35170, Izmir, Turkey.
| | - Tugba Arkan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Dokuz Eylul University Medical School, Inciralti, 35340, Izmir, Turkey
| | - Tuncay Kume
- Department of Biochemistry and Clinical Biochemistry, Dokuz Eylul University Medical School, Inciralti, 35340, Izmir, Turkey
| | - Fırat Bayraktar
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Dokuz Eylul University Medical School, Inciralti, 35340, Izmir, Turkey
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Narvaez-Sanchez R, Calderón JC, Vega G, Trillos MC, Ospina S. Skeletal muscle as a protagonist in the pregnancy metabolic syndrome. Med Hypotheses 2019; 126:26-37. [PMID: 31010495 DOI: 10.1016/j.mehy.2019.02.049] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Revised: 02/12/2019] [Accepted: 02/27/2019] [Indexed: 12/13/2022]
Abstract
The pregnant woman normally shows clinical manifestations similar to a metabolic syndrome (MS), due to her metabolic and hemodynamic adaptations in order to share nutrients with the child. If those adjustments are surpassed, a kind of pregnancy MS (PregMS) could appear, characterized by excessive insulin resistance and vascular maladaptation. Skeletal muscle (SKM) must be a protagonist in the PregMS: SKM strength and mass have been associated inversely with MS incidence in non-pregnant patients, and in pregnant women muscular activity modulates metabolic and vascular adaptations that favor better outcomes. Of note, a sedentary lifestyle affects exactly in the other way. Those effects may be explained not only by the old paradigm of SKM being a great energy consumer and store, but because it is an endocrine organ whose chronic activity or deconditioning correspondingly releases myokines modulating insulin sensitivity and cardiovascular adaptation, by direct or indirect mechanisms not well understood. In this document, we present evidence to support the concept of a PregMS and hypothesize on the role of the SKM mass, fiber types composition and myokines in its pathophysiology. Also, we discuss some exercise interventions in pregnancy as a way to test our hypotheses.
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Affiliation(s)
- Raul Narvaez-Sanchez
- Physiology and Biochemistry Research Group PHYSIS, Faculty of Medicine, University of Antioquia, Medellin, Colombia; Red iberoamericana de trastornos vasculares y del embarazo, RIVATREM, Colombia.
| | - Juan C Calderón
- Physiology and Biochemistry Research Group PHYSIS, Faculty of Medicine, University of Antioquia, Medellin, Colombia. http://www.udea.edu.co/physis
| | - Gloria Vega
- Physiology and Biochemistry Research Group PHYSIS, Faculty of Medicine, University of Antioquia, Medellin, Colombia. http://www.udea.edu.co/physis
| | - Maria Camila Trillos
- Physiology and Biochemistry Research Group PHYSIS, Faculty of Medicine, University of Antioquia, Medellin, Colombia. http://www.udea.edu.co/physis
| | - Sara Ospina
- Physiology and Biochemistry Research Group PHYSIS, Faculty of Medicine, University of Antioquia, Medellin, Colombia. http://www.udea.edu.co/physis
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Behboudi-Gandevani S, Ramezani Tehrani F, Rahmati M, Amiri M, Azizi F. Trend of various adiposity indices in women with and without history of gestational diabetes: a population-based cohort study. BMC Endocr Disord 2019; 19:24. [PMID: 30782162 PMCID: PMC6381680 DOI: 10.1186/s12902-019-0348-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 02/01/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Data of studies focusing on the trends of adiposity indices among women with prior gestational diabetes mellitus (GDM), are limited and controversial. The aim of this study was to compare overtime trends of adiposity indices in women with and without history of GDM, using data of the long term longitudinal population-based Tehran-Lipid and Glucose-Study (TLGS). METHODS A total of 3395 eligible women aged (20-50 years), including 801 women with prior history of GDM and 2594 non-GDM controls were recruited from among Tehran-Lipid and Glucose-Study participants. Generalized estimating equations were applied to assess the time trend of adiposity indices including obesity, central obesity, body mass index (BMI), lipid accumulation product index (LAP), visceral adiposity index (VAI) and a body shape index (ABSI) in women with prior GDM and the non-GDM groups after further adjustment for age and BMI. RESULTS Median follow-up years for the GDM and non-GDM groups were 12.12 and 11.62 years, respectively. Women with GDM at initiation had worse adiposity indices than their healthy counterparts. While overall odds of obesity in women with prior GDM were significantly higher those of the non-GDM groups (OR: 1.35; 95% CI, 1.03-1.7; P = 0.03), both these groups overtime revealed a positive trend in obesity (P trend < 0.001), an incremental trend which was less pronounced in GDM women (OR: 0.87; 95% CI, 0.80, 0.95; P interaction = 0.001). Women with prior GDM had higher odds of central obesity, compared to non-GDM groups (OR: 1.44; 95% CI, 1.06-1.96; P = 0.02) and showed a significant an incremental trend overtime for both groups (P trend < 0.001 for both) without statistically significant interaction in terms of their GDM status (P interaction = 0.134). Mean VAI in women with prior GDM was significantly higher than the non-GDM group (19.7, 95%CI: 6.24, 33.15, P = 0.004), although both groups overtime experienced a negative trend (- 10.9, 95%CI: -13.1, - 2.1, P < 0.001); the GDM group showed a higher decrease in VAI (mean changes: -6.62; 95% CI, - 11,-2.1; P interaction = 0.001). However overtime there was a positive trend in LAP and ABSI among both women with and without prior-GDM, though the mean changes were less obvious in women with prior GDM. CONCLUSION Women with prior GDM gained better control of their adiposity than non-GDM women. Nevertheless the increasing numbers of individuals with GDM and uncontrolled adiposity indices, require prompt attention be paid to the issue.
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Affiliation(s)
- Samira Behboudi-Gandevani
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fahimeh Ramezani Tehrani
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Maryam Rahmati
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mina Amiri
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Parvane Street, Yaman Street, Velenjak, Tehran, Iran
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