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Abdul-Rahman T, Roy P, Ahmed FK, Mueller-Gomez JL, Sarkar S, Garg N, Femi-Lawal VO, Wireko AA, Thaalibi HI, Hashmi MU, Dzebu AS, Banimusa SB, Sood A. The power of three: Retatrutide's role in modern obesity and diabetes therapy. Eur J Pharmacol 2024; 985:177095. [PMID: 39515565 DOI: 10.1016/j.ejphar.2024.177095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Revised: 10/19/2024] [Accepted: 10/31/2024] [Indexed: 11/16/2024]
Abstract
The increasing prevalence of obesity and type 2 diabetes mellitus has resulted in a significant challenge to public health throughout the globe. It required the development of novel therapeutic approaches. Retatrutide is a groundbreaking triple agonist that targets glucagon receptors, gastric inhibitory polypeptide, and glucagon-like peptide-1. Retatrutide's complex mechanism of action involves a synergistic interaction among these receptors, resulting in increased insulin secretion, improved glucose homeostasis, and refined appetite modulation. Clinical trials in phases 1 to 3 have demonstrated significant efficacy, highlighted by significant reductions in body weight and favorable glycemic control outcomes. Additionally, retatrutide shows promise in mitigating cardiovascular risk factors and addressing metabolic dysfunction-associated steatotic liver disease. However, careful attention is required to delineate its long-term safety profile, explore its potential in special populations, unravel its adjunctive therapeutic roles, and elucidate its mechanisms in pediatric cohorts. As a transformative therapeutic modality, retatrutide represents a beacon of hope, signifying transformative changes in the management landscape of obesity and type 2 diabetes mellitus (T2DM), and warranting continued exploration and refinement in clinical practice. This narrative review examines the therapeutic potential of retatrutide in the management of obesity and T2DM.
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Affiliation(s)
| | - Poulami Roy
- Department of Research, Toufik's World Medical Association, Sumy, Ukraine; Department of Medicine, North Bengal Medical College and Hospital, Siliguri, India
| | - Fatma Kamal Ahmed
- Department of Research, Toufik's World Medical Association, Sumy, Ukraine; University of Nairobi, Nairobi, Kenya
| | - Jann Ludwig Mueller-Gomez
- Department of Research, Toufik's World Medical Association, Sumy, Ukraine; Center for Research in Health Sciences (CICSA), Faculty of Medicine, Anahuac University North Campus, Huixquilucan, Mexico
| | - Sarmistha Sarkar
- Department of Research, Toufik's World Medical Association, Sumy, Ukraine; Department of Psychiatry, Community Clinical Research, Inc., Austin, TX, USA
| | - Neil Garg
- Department of Research, Toufik's World Medical Association, Sumy, Ukraine; Rowan-Virtua School of Osteopathic Medicine, One Medical Center Drive Stratford, New Jersey, USA
| | - Victor Oluwafemi Femi-Lawal
- Department of Research, Toufik's World Medical Association, Sumy, Ukraine; Department of Medicine and Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | | | - Hala Ibrahim Thaalibi
- Department of Research, Toufik's World Medical Association, Sumy, Ukraine; Beirut Arab University Faculty of Medicine, Beirut, Lebanon
| | - Muhammad Usman Hashmi
- Department of Research, Toufik's World Medical Association, Sumy, Ukraine; Department of Physiology, Rawalpindi Medical University, Rawalpindi, Pakistan
| | | | - Sewar Basheer Banimusa
- Department of Research, Toufik's World Medical Association, Sumy, Ukraine; Basic Medical Sciences, Yarmouk University, Irbid, Jordan
| | - Aayushi Sood
- Department of Medicine, The Wright Center for Graduate Medical Education, Scranton, PA, USA.
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Gonçalves B, Aires A, Oliveira I, Baltazar M, Cosme F, Afonso S, Pinto T, Anjos MR, Inês A, Morais MC, Vilela A, Silva AP. From Orchard to Wellness: Unveiling the Health Effects of Sweet Cherry Nutrients. Nutrients 2024; 16:3660. [PMID: 39519493 PMCID: PMC11547742 DOI: 10.3390/nu16213660] [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] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 10/23/2024] [Accepted: 10/25/2024] [Indexed: 11/16/2024] Open
Abstract
This review paper explores the multifaceted relationship between sweet cherry nutrients and human health, aiming to uncover the comprehensive impact of these bioactive compounds from orchard to wellness. Furthermore, it highlights how advanced crop techniques can be pivotal in optimizing these beneficial compounds. Synthesizing existing literature, the paper examines the diverse bioactive nutrients in sweet cherries, including antioxidants, polyphenols, vitamins, and minerals, and elucidating their mechanisms of action and potential health benefits. From antioxidant properties to anti-inflammatory effects, the paper elucidates how these nutrients may mitigate chronic diseases such as cardiovascular disorders, diabetes, and neurodegenerative conditions. Additionally, it explores their role in promoting gastrointestinal health, enhancing exercise recovery, and modulating sleep patterns. The review discusses emerging research on the potential anti-cancer properties of sweet cherry compounds, highlighting their promising role in cancer prevention and treatment. Furthermore, it delves into the impact of sweet cherry consumption on metabolic health, weight management, and skin health. By providing a comprehensive overview of the current understanding of sweet cherry nutrients and their health effects, this paper offers valuable insights for researchers, healthcare professionals, and consumers interested in utilizing nature's bounty for holistic wellness.
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Affiliation(s)
- Berta Gonçalves
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-of-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal; (A.A.); (I.O.); (M.B.); (S.A.); (T.P.); (M.R.A.); (M.C.M.); (A.P.S.)
| | - Alfredo Aires
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-of-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal; (A.A.); (I.O.); (M.B.); (S.A.); (T.P.); (M.R.A.); (M.C.M.); (A.P.S.)
| | - Ivo Oliveira
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-of-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal; (A.A.); (I.O.); (M.B.); (S.A.); (T.P.); (M.R.A.); (M.C.M.); (A.P.S.)
| | - Miguel Baltazar
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-of-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal; (A.A.); (I.O.); (M.B.); (S.A.); (T.P.); (M.R.A.); (M.C.M.); (A.P.S.)
| | - Fernanda Cosme
- Chemistry Research Centre-Vila Real (CQ-VR), University of Trás-of-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal; (F.C.); (A.I.); (A.V.)
| | - Sílvia Afonso
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-of-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal; (A.A.); (I.O.); (M.B.); (S.A.); (T.P.); (M.R.A.); (M.C.M.); (A.P.S.)
| | - Teresa Pinto
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-of-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal; (A.A.); (I.O.); (M.B.); (S.A.); (T.P.); (M.R.A.); (M.C.M.); (A.P.S.)
| | - Maria Rosário Anjos
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-of-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal; (A.A.); (I.O.); (M.B.); (S.A.); (T.P.); (M.R.A.); (M.C.M.); (A.P.S.)
| | - António Inês
- Chemistry Research Centre-Vila Real (CQ-VR), University of Trás-of-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal; (F.C.); (A.I.); (A.V.)
| | - Maria Cristina Morais
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-of-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal; (A.A.); (I.O.); (M.B.); (S.A.); (T.P.); (M.R.A.); (M.C.M.); (A.P.S.)
| | - Alice Vilela
- Chemistry Research Centre-Vila Real (CQ-VR), University of Trás-of-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal; (F.C.); (A.I.); (A.V.)
| | - Ana Paula Silva
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-of-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal; (A.A.); (I.O.); (M.B.); (S.A.); (T.P.); (M.R.A.); (M.C.M.); (A.P.S.)
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Busso D, González A, Santander N, Saavedra F, Quiroz A, Rivera K, González J, Olmos P, Marette A, Bazinet L, Illanes S, Enrione J. A Quinoa Protein Hydrolysate Fractionated by Electrodialysis with Ultrafiltration Membranes Improves Maternal and Fetal Outcomes in a Mouse Model of Gestational Diabetes Mellitus. Mol Nutr Food Res 2023; 67:e2300047. [PMID: 37667444 DOI: 10.1002/mnfr.202300047] [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: 01/27/2023] [Revised: 05/08/2023] [Indexed: 09/06/2023]
Abstract
SCOPE Quinoa intake exerts hypoglycemic and hypolipidemic effects in animals and humans. Although peptides from quinoa inhibit key enzymes involved in glucose homeostasis in vitro, their in vivo antidiabetic properties have not been investigated. METHODS AND RESULTS This study evaluated the effect of oral administration of a quinoa protein hydrolysate (QH) produced through enzymatic hydrolysis and fractionation by electrodialysis with ultrafiltration membrane (EDUF) (FQH) on the metabolic and pregnancy outcomes of Lepdb/+ pregnant mice, a preclinical model of gestational diabetes mellitus. The 4-week pregestational consumption of 2.5 mg mL-1 of QH in water prevented glucose intolerance and improves hepatic insulin signaling in dams, also reducing fetal weights. Sequencing and bioinformatic analyses of the defatted FQH (FQHD) identified 11 peptides 6-10 amino acids long that aligned with the quinoa proteome and exhibited putative anti-dipeptidyl peptidase-4 (DPP-IV) activity, confirmed in vitro in QH, FQH, and FDQH fractions. Peptides homologous to mouse and human proteins enriched for biological processes related to glucose metabolism are also identified. CONCLUSION Processing of quinoa protein may be used to develop a safe and effective nutritional intervention to control glucose intolerance during pregnancy. Further studies are required to confirm if this nutritional intervention is applicable to pregnant women.
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Affiliation(s)
- Dolores Busso
- Program of Reproductive Biology, Research and Innovation Center, School of Medicine, Faculty of Medicine, Universidad de los Andes, Santiago, 7550000, Chile
- Center of Interventional Medicine for Precision and Advanced Cellular Therapy (IMPACT), Universidad de los Andes, Santiago, 7550000, Chile
| | - Adrián González
- Biopolymer Research and Engineering Lab (BiopREL), Research and Innovation Center, School of Nutrition and Dietetics, Faculty of Medicine, Universidad de los Andes, Santiago, 7550000, Chile
| | - Nicolás Santander
- Health Science Institute, Universidad de O´Higgins, Rancagua, 2841959, Chile
| | - Fujiko Saavedra
- Program of Reproductive Biology, Research and Innovation Center, School of Medicine, Faculty of Medicine, Universidad de los Andes, Santiago, 7550000, Chile
| | - Alonso Quiroz
- PhD Program in Medical Sciences, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, 8320000, Chile
| | - Katherine Rivera
- PhD Program in Medical Sciences, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, 8320000, Chile
| | - Javier González
- Immersion in Science Program, School of Medicine, Faculty of Medicine, Universidad de los Andes, Santiago, 7550000, Chile
| | - Pablo Olmos
- Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, 8320000, Chile
| | - André Marette
- Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, Québec G1V 0A6, Canada
- Department of Anatomy and Physiology, Faculty of Medicine, Laval Hospital Research Center, Université Laval, Québec, Québec G1V 4G5, Canada
| | - Laurent Bazinet
- Department of Anatomy and Physiology, Faculty of Medicine, Laval Hospital Research Center, Université Laval, Québec, Québec G1V 4G5, Canada
- Department of Food Science and Nutrition, Laboratoire de Transformation Alimentaire et Procédés ÉlectroMembranaire (LTAPEM, Laboratory of Food Processing and Electro-Membrane Processes) Université Laval, Québec, Québec G1V 0A6, Canada
| | - Sebastián Illanes
- Program of Reproductive Biology, Research and Innovation Center, School of Medicine, Faculty of Medicine, Universidad de los Andes, Santiago, 7550000, Chile
- Center of Interventional Medicine for Precision and Advanced Cellular Therapy (IMPACT), Universidad de los Andes, Santiago, 7550000, Chile
| | - Javier Enrione
- Center of Interventional Medicine for Precision and Advanced Cellular Therapy (IMPACT), Universidad de los Andes, Santiago, 7550000, Chile
- Biopolymer Research and Engineering Lab (BiopREL), Research and Innovation Center, School of Nutrition and Dietetics, Faculty of Medicine, Universidad de los Andes, Santiago, 7550000, Chile
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Hu Y, Wang J, Wang J, Chen W, Zhang Q. DPP-4 Inhibitor Improved the Cognitive Function in Diabetic Rats. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:8280389. [PMID: 39280108 PMCID: PMC11401724 DOI: 10.1155/2022/8280389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 03/02/2022] [Indexed: 09/18/2024]
Abstract
Diabetes-associated cognitive dysfunction is a major problem of the international community. Dipeptidyl peptidase-4 (DPP-4) inhibitors are drugs with hypoglycemic effect widely used in diabetic treatment in clinic. In this article, we studied the effect of the DPP-4 inhibitor saxagliptin on cognitive function in diabetic rats. Firstly, to observe cognitive dysfunction caused by diabetes, we built the diabetic rat model. Subsequently, the effect of diabetes on cognitive function was evaluated by Morris Water Maze Task. Thirdly, the mechanism of the alleviation effect of DPP-4 inhibitor on cognitive dysfunction was investigated. Specifically, (1) the anti-inflammation mechanism was revealed by quantifying the accumulation of the inflammatory factor interleukin-1β (IL-1β) in the hippocampus area by western blotting and the glial fibrillary acidic protein (GFAP) by immunohistochemistry; (2) the anti-tau phosphorylation mechanism was revealed by quantifying phosphorylated tau by western blotting. This work represents the first study demonstrating the alleviation effect of DPP-4 inhibitor on cognitive dysfunction caused by diabetes. Results obtained here could be useful to seeking for a medical solution with high efficacy to the diabetes-associated cognitive dysfunction.
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Affiliation(s)
- Ying Hu
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
- Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang, Jiangxi 330006, China
- Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, Jiangxi 330006, China
| | - Jiancheng Wang
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
- Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang, Jiangxi 330006, China
- Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, Jiangxi 330006, China
| | - Jiao Wang
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
- Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang, Jiangxi 330006, China
- Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, Jiangxi 330006, China
| | - Wen Chen
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
- Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang, Jiangxi 330006, China
- Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, Jiangxi 330006, China
| | - Qin Zhang
- Department of Anesthesiology, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
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Vignati E, Lipska M, Dunwell JM, Caccamo M, Simkin AJ. Fruit Development in Sweet Cherry. PLANTS (BASEL, SWITZERLAND) 2022; 11:plants11121531. [PMID: 35736682 PMCID: PMC9227597 DOI: 10.3390/plants11121531] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/02/2022] [Accepted: 06/04/2022] [Indexed: 05/19/2023]
Abstract
Fruits are an important source of vitamins, minerals and nutrients in the human diet. They also contain several compounds of nutraceutical importance that have significant antioxidant and anti-inflammatory roles, which can protect the consumer from diseases, such as cancer, and cardiovascular disease as well as having roles in reducing the build-up of LDL-cholesterol in blood plasma and generally reduce the risks of disease and age-related decline in health. Cherries contain high concentrations of bioactive compounds and minerals, including calcium, phosphorous, potassium and magnesium, and it is, therefore, unsurprising that cherry consumption has a positive impact on health. This review highlights the development of sweet cherry fruit, the health benefits of cherry consumption, and the options for increasing consumer acceptance and consumption.
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Affiliation(s)
- Edoardo Vignati
- NIAB, New Road, East Malling ME19 6BJ, UK; (E.V.); (M.L.)
- School of Agriculture, Policy and Development, University of Reading, Whiteknights, Reading RG6 6EU, UK;
| | - Marzena Lipska
- NIAB, New Road, East Malling ME19 6BJ, UK; (E.V.); (M.L.)
| | - Jim M. Dunwell
- School of Agriculture, Policy and Development, University of Reading, Whiteknights, Reading RG6 6EU, UK;
| | - Mario Caccamo
- NIAB, Cambridge Crop Research, Lawrence Weaver Road, Cambridge CB3 0LE, UK;
| | - Andrew J. Simkin
- NIAB, New Road, East Malling ME19 6BJ, UK; (E.V.); (M.L.)
- School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK
- Correspondence:
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Nedosugova LV, Markina YV, Bochkareva LA, Kuzina IA, Petunina NA, Yudina IY, Kirichenko TV. Inflammatory Mechanisms of Diabetes and Its Vascular Complications. Biomedicines 2022; 10:biomedicines10051168. [PMID: 35625904 PMCID: PMC9138517 DOI: 10.3390/biomedicines10051168] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 05/13/2022] [Accepted: 05/16/2022] [Indexed: 12/14/2022] Open
Abstract
The main cause of death in patients with type 2 DM is cardiovascular complications resulting from the progression of atherosclerosis. The pathophysiology of the association between diabetes and its vascular complications is complex and multifactorial and closely related to the toxic effects of hyperglycemia that causes increased generation of reactive oxygen species and promotes the secretion of pro-inflammatory cytokines. Subsequent oxidative stress and inflammation are major factors of the progression of type 2 DM and its vascular complications. Data on the pathogenesis of the development of type 2 DM and associated cardiovascular diseases, in particular atherosclerosis, open up broad prospects for the further development of new diagnostic and therapeutic approaches.
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Affiliation(s)
- Lyudmila V. Nedosugova
- Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia; (L.V.N.); (L.A.B.); (I.A.K.); (N.A.P.); (I.Y.Y.)
| | - Yuliya V. Markina
- Petrovsky National Research Center of Surgery, 119991 Moscow, Russia;
| | - Leyla A. Bochkareva
- Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia; (L.V.N.); (L.A.B.); (I.A.K.); (N.A.P.); (I.Y.Y.)
| | - Irina A. Kuzina
- Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia; (L.V.N.); (L.A.B.); (I.A.K.); (N.A.P.); (I.Y.Y.)
| | - Nina A. Petunina
- Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia; (L.V.N.); (L.A.B.); (I.A.K.); (N.A.P.); (I.Y.Y.)
| | - Irina Y. Yudina
- Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia; (L.V.N.); (L.A.B.); (I.A.K.); (N.A.P.); (I.Y.Y.)
- Petrovsky National Research Center of Surgery, 119991 Moscow, Russia;
| | - Tatiana V. Kirichenko
- Petrovsky National Research Center of Surgery, 119991 Moscow, Russia;
- Chazov National Medical Research Center of Cardiology, 121552 Moscow, Russia
- Correspondence:
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Stanzione R, Forte M, Cotugno M, Bianchi F, Marchitti S, Busceti CL, Fornai F, Rubattu S. Uncoupling Protein 2 as a Pathogenic Determinant and Therapeutic Target in Cardiovascular and Metabolic Diseases. Curr Neuropharmacol 2022; 20:662-674. [PMID: 33882809 PMCID: PMC9878956 DOI: 10.2174/1570159x19666210421094204] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 03/10/2021] [Accepted: 04/16/2021] [Indexed: 11/22/2022] Open
Abstract
Uncoupling protein 2 (UCP2) is a mitochondrial protein that acts as an anion carrier. It is involved in the regulation of several processes, including mitochondrial membrane potential, generation of reactive oxygen species within the inner mitochondrial membrane and calcium homeostasis. UCP2 expression can be regulated at different levels: genetic (gene variants), transcriptional [by peroxisome proliferator-activated receptors (PPARs) and microRNAs], and post-translational. Experimental evidence indicates that activation of UCP2 expression through the AMPK/PPAR-α axis exerts a protective effect toward renal damage and stroke occurrence in an animal model of ischemic stroke (IS) associated with hypertension. UCP2 plays a key role in heart diseases (myocardial infarction and cardiac hypertrophy) and metabolic disorders (obesity and diabetes). In humans, UCP2 genetic variants (-866G/A and Ala55Val) associate with an increased risk of type 2 diabetes mellitus and IS development. Over the last few years, many agents that modulate UCP2 expression have been identified. Some of them are natural compounds of plant origin, such as Brassica oleracea, curcumin, berberine and resveratrol. Other molecules, currently used in clinical practice, include anti-diabetic (gliptin) and chemotherapeutic (doxorubicin and taxol) drugs. This evidence highlights the relevant role of UCP2 for the treatment of a wide range of diseases, which affect the national health systems of Western countries. We will review current knowledge on the physiological and pathological implications of UCP2 with particular regard to cardiovascular and metabolic disorders and will focus on the available therapeutic approaches affecting UCP2 level for the treatment of human diseases.
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Affiliation(s)
- Rosita Stanzione
- IRCCS Neuromed, Pozzilli Isernia, Italy,,Address correspondence to these authors at the IRCCS Neuromed, Località Camerelle, 86077 Pozzilli, Is, Italy; Tel: +390865915224/23; Fax: +390865927575; E-mail: and Clinical and Molecular Medicine Department, School of Medicine and Psychology, Sapienza University of Rome, Ospedale S.Andrea, 00189 Rome, Italy; Tel: +390865915224/23; Fax: +390865927575; E-mail:
| | | | | | | | | | | | - Francesco Fornai
- IRCCS Neuromed, Pozzilli Isernia, Italy,,Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Speranza Rubattu
- IRCCS Neuromed, Pozzilli Isernia, Italy,,Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, Rome, Italy,Address correspondence to these authors at the IRCCS Neuromed, Località Camerelle, 86077 Pozzilli, Is, Italy; Tel: +390865915224/23; Fax: +390865927575; E-mail: and Clinical and Molecular Medicine Department, School of Medicine and Psychology, Sapienza University of Rome, Ospedale S.Andrea, 00189 Rome, Italy; Tel: +390865915224/23; Fax: +390865927575; E-mail:
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Kaur N, Kumar V, Nayak SK, Wadhwa P, Kaur P, Sahu SK. Alpha-amylase as molecular target for treatment of diabetes mellitus: A comprehensive review. Chem Biol Drug Des 2021; 98:539-560. [PMID: 34173346 DOI: 10.1111/cbdd.13909] [Citation(s) in RCA: 92] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/31/2021] [Accepted: 06/06/2021] [Indexed: 01/13/2023]
Abstract
The alpha (α)-amylase is a calcium metalloenzyme that aids digestion by breaking down polysaccharide molecules into smaller ones such as glucose and maltose. In addition, the enzyme causes postprandial hyperglycaemia and blood glucose levels to rise. α-Amylase is a well-known therapeutic target for the treatment and maintenance of postprandial blood glucose elevations. Various enzymatic inhibitors, such as acarbose, miglitol and voglibose, have been found to be effective in targeting this enzyme, prompting researchers to express an interest in developing potent alpha-amylase inhibitor molecules. The review mainly focused on designing different derivatives of drug molecules such as benzofuran hydrazone, indole hydrazone, spiroindolone, benzotriazoles, 1,3-diaryl-3-(arylamino) propan-1-one, oxadiazole and flavonoids along with their target-receptor interactions, IC50 values and other biological activities.
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Affiliation(s)
- Navjot Kaur
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Vanktesh Kumar
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Surendra Kumar Nayak
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Pankaj Wadhwa
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Paranjit Kaur
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Sanjeev Kumar Sahu
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
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Rezki A, Fysekidis M, Chiheb S, Vicaut E, Cosson E, Valensi P. Acute and long-term effects of saxagliptin on post-prandial glycemic response in obese patients with impaired glucose tolerance. Nutr Metab Cardiovasc Dis 2021; 31:1257-1266. [PMID: 33618922 DOI: 10.1016/j.numecd.2020.12.025] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 11/25/2020] [Accepted: 12/22/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Dipeptidyl-peptidase inhibitors might be useful in type 2 diabetes prevention. ACCES (ACute and Chronic Effects of Saxagliptin) was a randomized, placebo-controlled, double-blind, controlled phase 2, pilot study aiming to examine in obese patients with impaired glucose tolerance (IGT) the acute effects and the effects after 12 weeks of treatment by saxagliptin on glucose levels at fasting and postprandially after a standard breakfast, and on glucose tolerance. METHODS AND RESULTS We included 24 obese patients with IGT. Patients were randomized to receive saxagliptin 5 mg or placebo in the morning. The treatment was taken on Visit 1 before breakfast, then continued for 12 weeks. Biochemical measurements were performed before, one, two and three hours after a standard breakfast including 75 g of carbohydrates, during Visit 1 and Visit 2 (12 weeks). Glucose variability (GV) was evaluated at Visit 1 from 24-h continuous glucose monitoring including the breakfast. A second OGTT was performed at Visit 3 (3-5 days after Visit 2). Compared with placebo-treated patients, saxagliptin-treated patients had lower 1 h and 2 h post-meal plasma glucose levels at Visit 1 and similar changes at Visit 2 (p < 0.01 to p < 0.004), with lower GV indexes after breakfast at Visit 1. At Visit 3, all patients but one in saxagliptin group and only 4 patients in placebo group turned to normal glucose tolerance. Lower glucose response to breakfast at Visit 1 was predictive of recovery of glucose tolerance. CONCLUSION Saxagliptin has metabolically beneficial effects in glucose-intolerant obese patients by significantly lowering postprandial blood glucose levels. CLINICAL TRIAL REGISTRATION NUMBER NCT01521312: https://clinicaltrials.gov/ct2/show/NCT01521312.
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Affiliation(s)
- Amel Rezki
- Department of Endocrinology, Diabetology, Nutrition, Jean Verdier Hospital, AP-HP, CRNH-IdF, CINFO, Paris Nord University, Sorbonne Paris Cité, Bondy, France; Sorbonne Paris Cité, UMR U1153 Inserm/U1125 Inra/Cnam/Université Paris 13, Bobigny, France
| | - Marinos Fysekidis
- Department of Endocrinology, Diabetology, Nutrition, Jean Verdier Hospital, AP-HP, CRNH-IdF, CINFO, Paris Nord University, Sorbonne Paris Cité, Bondy, France; Sorbonne Paris Cité, UMR U1153 Inserm/U1125 Inra/Cnam/Université Paris 13, Bobigny, France
| | - Sabrina Chiheb
- Department of Endocrinology, Diabetology, Nutrition, Jean Verdier Hospital, AP-HP, CRNH-IdF, CINFO, Paris Nord University, Sorbonne Paris Cité, Bondy, France
| | - Eric Vicaut
- Clinical Research Unit, Lariboisière-St Louis, Fernand Widal Hospital, APHP, Paris, France
| | - Emmanuel Cosson
- Department of Endocrinology, Diabetology, Nutrition, Jean Verdier Hospital, AP-HP, CRNH-IdF, CINFO, Paris Nord University, Sorbonne Paris Cité, Bondy, France; Sorbonne Paris Cité, UMR U1153 Inserm/U1125 Inra/Cnam/Université Paris 13, Bobigny, France
| | - Paul Valensi
- Department of Endocrinology, Diabetology, Nutrition, Jean Verdier Hospital, AP-HP, CRNH-IdF, CINFO, Paris Nord University, Sorbonne Paris Cité, Bondy, France.
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Song A, Jiang A, Xiong W, Zhang C. The Role of CXCL12 in Kidney Diseases: A Friend or Foe? KIDNEY DISEASES 2021; 7:176-185. [PMID: 34179113 DOI: 10.1159/000514913] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 01/28/2021] [Indexed: 12/25/2022]
Abstract
Background Chemokines are a family of proteins mainly mediating the homing and migration of various cells. The CXC chemokine CXCL12 is a member of low-weight-molecular chemokines. In the kidney, CXCL12 is pivotal for renal development and exerts a modulatory effect in kidney diseases under different etiologic settings by binding with CXC chemokine receptor 4 (CXCR4) or CXC chemokine receptor 7 (CXCR7). Besides, CXCL12 also exerts homeostasis influence in diverse physical conditions and various pathological situations. Thus, we conclude the complicated relationship between CXCL12 and kidney diseases in this review. Summary In renal development, CXCL12 contributes a lot to nephrogenesis and the formation of renal vasculature via correlating with CXCR4. CXCL12 also plays an essential role in renal recovery from acute kidney injury. However, the CXCL12/CXCR4 axis plays a dual regulatory role in the initiation and development of diabetic kidney disease as well as chronic allogeneic nephropathy after kidney transplantation through dialectical consideration. Additionally, the CXCL12/CXCR4 link is considered as a new risk factor for lupus nephritis and renal cell carcinoma. Key Messages Plenty of studies have presented the influence of CXCL12 and the relation with corresponding receptors in diverse biological and pathological statuses. Simultaneously, some drugs and antagonists targeting CXCL12/CXCR4 axis effectively treat various kidney diseases. However, more researches are needed to explore thorough influence and mechanisms, providing more cues for clinical treatments.
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Affiliation(s)
- Anni Song
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Anni Jiang
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Xiong
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chun Zhang
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Abdalla MA, Deshmukh H, Atkin S, Sathyapalan T. The potential role of incretin-based therapies for polycystic ovary syndrome: a narrative review of the current evidence. Ther Adv Endocrinol Metab 2021; 12:2042018821989238. [PMID: 33552465 PMCID: PMC7844452 DOI: 10.1177/2042018821989238] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 01/03/2021] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. Metabolic consequences associated with PCOS include, but are not limited to, insulin resistance (IR), type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). This narrative review aims to provide a comprehensive overview of the potential therapeutic roles of the incretin-based therapies in the management of PCOS. METHODS We performed a systematic search of databases including PubMed, MEDLINE and EMBASE up to 1 October 2020. We developed a search string of medical subject headings (MeSH) including the terms PCOS, incretin mimetics, glucagon-like peptide-1 (GLP-1), glucagon-like peptide-1 receptor antagonists (GLP-1 RAs), liraglutide, exenatide, semaglutide, dipeptidyl peptidase-4 (DPP-4) inhibitors, combined with IR, testosterone and sex hormone-binding globulin (SHBG). RESULTS We identified 854 relevant articles and, after the initial screening, eight interventional animal studies, one observational animal study, 14 interventional human studies, two case-control studies and one systematic review were included. These studies showed the potential significant roles of GLP-1 RAs and DPP-4 inhibitors in the management of PCOS, with significant improvements in the metabolic parameters, including substantial weight reduction and improved insulin sensitivity. These agents also improved the hormonal parameters through decreased free androgen and increased SHBG. Moreover, they improved menstrual regularity, increased fertility with enhanced ovulation and pregnancy in obese women with PCOS. CONCLUSION GLP-1 RAs and DPP-4 inhibitors have a promising therapeutic role in PCOS; however, larger clinical trials are needed to establish the role of incretin-based therapies in the management of PCOS.
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Affiliation(s)
- Mohammed Altigani Abdalla
- Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, UK
| | - Harshal Deshmukh
- Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, UK
| | - Stephen Atkin
- School of Postgraduate Studies and Research, RCSI Medical University of Bahrain, Kingdom of Bahrain
| | - Thozhukat Sathyapalan
- Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, UK
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12
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Kaneto H, Koshida R, Baxter M. Fixed-ratio combination of basal insulin and glucagon-like peptide-1 receptor agonists in the treatment of Japanese people with type 2 diabetes: An innovative solution to a complex therapeutic challenge. Diabetes Obes Metab 2020; 22 Suppl 4:24-34. [PMID: 32436323 DOI: 10.1111/dom.14095] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 05/12/2020] [Accepted: 05/19/2020] [Indexed: 12/13/2022]
Abstract
Over 10 million people in Japan have known or suspected type 2 diabetes (T2D), and this number is expected to rise. Although many people require therapy escalation because of the progressive nature of T2D, this appears to be suboptimal in Japanese real-world clinical practice. Insulin therapy tends to be introduced only when glycaemic control is very poor (mean glycated haemoglobin >9%). Although basal insulin therapy is effective in reducing fasting plasma glucose (FPG), postprandial plasma glucose often remains uncontrolled. Basal-bolus insulin regimens are complex and carry the risk of weight gain and hypoglycaemia. Recently, fixed-ratio combinations (FRCs) of BI and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown efficacy in reducing both FPG and postprandial plasma glucose with a single injection and without increased risk of hypoglycaemia or weight gain. IDegLira, a titratable FRC of insulin degludec (100 U/mL) and liraglutide, is currently available in Japan and the United States/European Union at a ratio of 1 U (unit):0.036 mg. iGlarLixi (insulin glargine 100 U/mL and lixisenatide at a ratio of 1:1 (20 U/20 μg) has recently been approved in Japan. Phase 3 trials in Japan for IDegLira (DUAL Japan) and iGlarLixi (LixiLan JP) have shown that both FRCs are efficacious. This review provides an overview of IDegLira and iGlarLixi (Japanese formulation) and considers their potential use as new therapeutic options to address the clinical need for early glycaemic control in Japanese people with T2D.
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Affiliation(s)
- Hideaki Kaneto
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan
| | | | - Mike Baxter
- Medical Affairs, Sanofi, Reading, UK
- Department of Diabetes and Endocrinology, University of Swansea, Swansea, UK
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Abstract
There remains an ongoing controversy regarding the safety of dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of developing heart failure (HF). In addition, none of the animal studies suggested a mechanism for the DPP-4 inhibitors and HF risk. To date, advances in pharmacogenomics have enabled the identification of genetic variants in DPP-4 gene. Studies have shown that genetic polymorphisms in the gene encoding DPP-4 may be associated with potential pathways involved in HF risk. This review discusses the contradictory findings of DPP-4 inhibitors and HF and a potential role for pharmacogenomics. Pharmacogenomics of DPP-4 inhibitors is promising, and genetic information from randomized control trials is urgently needed to gain a full understanding of the safety of DPP-4 inhibitors and the risk of HF.
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14
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Marx D, Wingen LM, Schnakenburg G, Müller CE, Scholz MS. Fast, Efficient, and Versatile Synthesis of 6-amino-5-carboxamidouracils as Precursors for 8-Substituted Xanthines. Front Chem 2019; 7:56. [PMID: 30834241 PMCID: PMC6387921 DOI: 10.3389/fchem.2019.00056] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 01/21/2019] [Indexed: 12/22/2022] Open
Abstract
Substituted xanthine derivatives are important bioactive molecules. Herein we report on a new, practical synthesis of 6-amino-5-carboxamidouracils, the main building blocks for the preparation of 8-substituted xanthines, by condensation of 5,6-diaminouracil derivatives and various carboxylic acids using the recently developed non-hazardous coupling reagent COMU (1-[(1-(cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinomethylene)]methanaminium hexafluorophosphate). Optimized reaction conditions led to the precipitation of pure products after only 5 to 10 min of reaction time. The method tolerates a variety of substituted 5,6-diaminouracil and carboxylic acid derivatives as starting compounds resulting in most cases in more than 80% isolated yield. Regioselectivity of the reaction yielding only the 5-carboxamido-, but not the 6-carboxamidouracil derivatives, was unambiguously confirmed by single X-ray crystallography and multidimensional NMR experiments. The described method represents a convenient, fast access to direct precursors of 8-substituted xanthines under mild conditions without the necessity of hazardous coupling or chlorinating reagents.
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Affiliation(s)
- Daniel Marx
- Pharmaceutical Chemistry 1, Pharmaceutical Institute, University of Bonn, Bonn, Germany
| | - Lukas M Wingen
- Pharmaceutical Chemistry 1, Pharmaceutical Institute, University of Bonn, Bonn, Germany
| | - Gregor Schnakenburg
- Department of Chemistry, Institute of Inorganic Chemistry, University of Bonn, Bonn, Germany
| | - Christa E Müller
- Pharmaceutical Chemistry 1, Pharmaceutical Institute, University of Bonn, Bonn, Germany
| | - Matthias S Scholz
- Pharmaceutical Chemistry 1, Pharmaceutical Institute, University of Bonn, Bonn, Germany
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15
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Choi MJ. Taurine May Modulate Bone in Cholesterol Fed Estrogen Deficiency-Induced Rats. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 975 Pt 2:1093-1102. [PMID: 28849525 DOI: 10.1007/978-94-024-1079-2_87] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Taurine is thought to affect bone in rats favorably. However, studies on the actions of this estrogen deficiency and high cholesterol diet factors on the bone metabolism are limited. In this study, the protective effect of taurine on bone was determined. Thirty-two 42 days old female SD rats were placed in individual stainless cages. Given to rats was fed to chow (Samyang Corporation, South Korea) and deionized water for a 4 days adaptation period. After the period of adaptation, Half of the rats were induced estrogen deficiency model by ovariectomy (OVX), and the left rats with sham-operated were used control (SHAM). For six weeks, the OVX and SHAM rats had separately a 2% taurine supplemented diet with ad libitum in both the water and the food. DEXA for small animals (PIXImus, GE Lunar co, Wisconsin) was used to determine spinal and femoral bone. The concentrations of serum calcium and phosphorus were also measured. The monitoring of bone formation was done by determining the serum ALP and osteocalcin. Urinary DPD the values were determined as index of bone resorption. Statistical measure was done with SAS (version 9.3). A lower overall intake of the daily food was observed in non-ovariectomized rats than in the OVX rats. At sacrifice, a much greater body weight was observed in ovariectomized group compare to non-operated group. That difference was absent in both fed taurine SHAM and OVX rats. Serum calcium and phosphorus were not statistically different by taurine supplementation. Urinary excretion of calcium was not effected by taurine supplementation. Serum ALP and was significantly decreased by taurine in OVX rats (p < 0.05). For the spine BMD and BMC, there was no difference among SHAM and OVX rats by taurine. Spine BMC per body weight of taurine groups were higher than control groups (p < 0.1). No significant difference was observed after taurine supplementation in femur BMD and BMC. The analysis of the results suggest that taurine supplementation modulates the bone mineral contents in postmenopausal model rats fed with high cholesterol diet.
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Affiliation(s)
- Mi-Ja Choi
- Department of Food and Nutrition, Keimyung University, Daegu, South Korea.
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16
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Kelley DS, Adkins Y, Laugero KD. A Review of the Health Benefits of Cherries. Nutrients 2018; 10:nu10030368. [PMID: 29562604 PMCID: PMC5872786 DOI: 10.3390/nu10030368] [Citation(s) in RCA: 100] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Revised: 03/12/2018] [Accepted: 03/14/2018] [Indexed: 01/11/2023] Open
Abstract
Increased oxidative stress contributes to development and progression of several human chronic inflammatory diseases. Cherries are a rich source of polyphenols and vitamin C which have anti-oxidant and anti-inflammatory properties. Our aim is to summarize results from human studies regarding health benefits of both sweet and tart cherries, including products made from them (juice, powder, concentrate, capsules); all referred to as cherries here. We found 29 (tart 20, sweet 7, unspecified 2) published human studies which examined health benefits of consuming cherries. Most of these studies were less than 2 weeks of duration (range 5 h to 3 months) and served the equivalent of 45 to 270 cherries/day (anthocyanins 55–720 mg/day) in single or split doses. Two-thirds of these studies were randomized and placebo controlled. Consumption of cherries decreased markers for oxidative stress in 8/10 studies; inflammation in 11/16; exercise-induced muscle soreness and loss of strength in 8/9; blood pressure in 5/7; arthritis in 5/5, and improved sleep in 4/4. Cherries also decreased hemoglobin A1C (HbA1C), Very-low-density lipoprotein (VLDL) and triglycerides/high-density lipoprotein (TG/HDL) in diabetic women, and VLDL and TG/HDL in obese participants. These results suggest that consumption of sweet or tart cherries can promote health by preventing or decreasing oxidative stress and inflammation.
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Affiliation(s)
- Darshan S Kelley
- US Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA 95616, USA.
- Department of Nutrition, University of California, Davis, CV 95616, USA.
| | - Yuriko Adkins
- US Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA 95616, USA.
- Department of Nutrition, University of California, Davis, CV 95616, USA.
| | - Kevin D Laugero
- US Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA 95616, USA.
- Department of Nutrition, University of California, Davis, CV 95616, USA.
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17
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Tao T, Wu P, Wang Y, Liu W. Comparison of glycemic control and β-cell function in new onset T2DM patients with PCOS of metformin and saxagliptin monotherapy or combination treatment. BMC Endocr Disord 2018; 18:14. [PMID: 29482528 PMCID: PMC5828487 DOI: 10.1186/s12902-018-0243-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Accepted: 02/19/2018] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Impaired insulin activity in women with polycystic ovary syndrome might differ from that seen in type 2 diabetes mellitus without polycystic ovary syndrome. This study was designed to compare the effects of treatment with metformin, saxagliptin, and their combination in newly diagnosed women with type 2 diabetes mellitus and polycystic ovary syndrome in China. METHODS A total of 75 newly diagnosed patients from Shanghai, China with type 2 diabetes mellitus and polycystic ovary syndrome were included in this randomized, parallel, open-label study. All patients received treatment for 24 weeks with metformin, saxagliptin, or their combination. Patients were allocated to one of three treatment groups by a computer-generated code that facilitated equal patient distribution of 25 patients per group. The primary outcome was a change in glycemic control and β-cell function. RESULTS A total of 63 patients completed the study (n = 21, for each group). The reduction in hemoglobin A1c was significant in the combination group, compared to the monotherapy groups (saxagliptin vs. combination treatment vs. metformin: - 1.1 vs. -1.3 vs. -1.1%, P = 0.016), whereas it was comparable between the metformin and saxagliptin groups (P > 0.05). Saxagliptin, metformin, and the combination treatment significantly reduced the homeostasis model assessment- insulin resistance index and increased the deposition index (P < 0.01 for all). However, no significant change was observed in the homeostasis model assessment- β-cell function among the metformin and combination groups, and no significant changes were observed in the insulinogenic index among all three groups (P > 0.05 for all). In addition, saxagliptin and metformin treatments significantly reduced body mass index and high-sensitivity C-reactive protein levels (P < 0.01 for both). CONCLUSIONS Saxagliptin and metformin were comparably effective in regulating weight loss, glycemic control, and β-cell function, improving lipid profiles, and reducing inflammation in newly diagnosed type 2 diabetes mellitus patients with polycystic ovary syndrome. TRIAL REGISTRATION ChiCTR-IPR-17011120 (retrospectively registered on 2017-04-12).
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Affiliation(s)
- Tao Tao
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127 China
| | - Peihong Wu
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127 China
| | - Yuying Wang
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127 China
| | - Wei Liu
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127 China
- Shanghai Key laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127 China
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Design of potent dipeptidyl peptidase IV (DPP-4) inhibitors by employing a strategy to form a salt bridge with Lys554. Bioorg Med Chem Lett 2017; 27:3565-3571. [PMID: 28579121 DOI: 10.1016/j.bmcl.2017.05.048] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Revised: 05/09/2017] [Accepted: 05/16/2017] [Indexed: 12/28/2022]
Abstract
We report a design strategy to obtain potent DPP-4 inhibitors by incorporating salt bridge formation with Lys554 in the S1' pocket. By applying the strategy to the previously identified templates, quinoline 4 and pyridines 16a, 16b, and 17 have been identified as subnanomolar or nanomolar inhibitors of human DPP-4. Docking studies suggested that a hydrophobic interaction with Tyr547 as well as the salt bridge interaction is important for the extremely high potency. The design strategy would be useful to explore a novel design for DPP-4 inhibitors having a distinct structure with a unique binding mode.
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19
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Hassan SSU, Shaikh AL. Marine actinobacteria as a drug treasure house. Biomed Pharmacother 2017; 87:46-57. [DOI: 10.1016/j.biopha.2016.12.086] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2016] [Revised: 12/20/2016] [Accepted: 12/20/2016] [Indexed: 01/19/2023] Open
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20
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Adisakwattana S. Cinnamic Acid and Its Derivatives: Mechanisms for Prevention and Management of Diabetes and Its Complications. Nutrients 2017; 9:nu9020163. [PMID: 28230764 PMCID: PMC5331594 DOI: 10.3390/nu9020163] [Citation(s) in RCA: 175] [Impact Index Per Article: 21.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Revised: 02/11/2017] [Accepted: 02/16/2017] [Indexed: 02/06/2023] Open
Abstract
With recent insight into the development of dietary supplements and functional foods, search of effective phytochemical compounds and their mechanisms involved in prevention and management of diabetes and its complications are now being assessed. Cinnamic acid and its derivatives occur naturally in high levels of plant-based foods. Among various biological activities, cinnamic acid and its derivatives are associated with a beneficial influence on diabetes and its complications. The aim of the review is to summarize the potential mechanisms of these compounds for prevention and management of diabetes and its complications. Based on several in vitro studies and animal models, cinnamic acid and its derivatives act on different mechanism of actions, including stimulation of insulin secretion, improvement of pancreatic β-cell functionality, inhibition of hepatic gluconeogenesis, enhanced glucose uptake, increased insulin signaling pathway, delay of carbohydrate digestion and glucose absorption, and inhibition of protein glycation and insulin fibrillation. However, due to the limited intestinal absorption being a result of low bioavailability of cinnamic acid and its derivatives, current improvement efforts with entrapping into solid and liquid particles are highlighted. Further human clinical studies are needed to clarify the effects of cinnamic acid and its derivatives in diabetic patients.
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Affiliation(s)
- Sirichai Adisakwattana
- Department of Nutrition and Dietetics, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
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21
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Pinar G, Kaplan S, Pinar T, Akalin A, Abay H, Akyol M, Sezer N, Akkus S, Sariyildiz S, RN SD. The prevalence and risk factors for osteoporosis among 18- to 49-year-old Turkish women. Women Health 2016; 57:1080-1097. [DOI: 10.1080/03630242.2016.1243604] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
- Gul Pinar
- Faculty of Health Sciences, Nursing Department, Yildirim Beyazit University, Ankara, Turkey
| | - Sena Kaplan
- Faculty of Health Sciences, Nursing Department, Yildirim Beyazit University, Ankara, Turkey
| | - Tevfik Pinar
- Institute of Public Health, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Ayse Akalin
- Faculty of Health Sciences, Nursing Department, Yildirim Beyazit University, Ankara, Turkey
| | - Halime Abay
- Faculty of Health Sciences, Nursing Department, Yildirim Beyazit University, Ankara, Turkey
| | - Mesut Akyol
- Faculty of Medicine, Department of Biostatistics and Medical Informatics, Yildirim Beyazit University, Ankara, Turkey
| | - Nebahat Sezer
- Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Yildirim Beyazit University, Atatürk Training and Research Hospital, Ankara, Turkey
| | - Selami Akkus
- Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Yildirim Beyazit University, Atatürk Training and Research Hospital, Ankara, Turkey
| | - Salim Sariyildiz
- Department of Chest Diseases, Cubuk Halil Sıvgın State Hospital, Ankara, Turkey
| | - Semra Dinc, RN
- Nursing Department, Cubuk Halil Sıvgın State Hospital, Ankara, Turkey
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Hemmingsen B, Krogh J, Metzendorf MI, Richter B. Dipeptidyl-peptidase (DPP)-4 inhibitors or glucagon-like peptide (GLP)-1 analogues for prevention or delay of type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2016. [DOI: 10.1002/14651858.cd012204] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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23
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Chen Z, Hao J, Wang L, Wang Y, Kong F, Zhu W. New α-glucosidase inhibitors from marine algae-derived Streptomyces sp. OUCMDZ-3434. Sci Rep 2016; 6:20004. [PMID: 26822662 PMCID: PMC4731795 DOI: 10.1038/srep20004] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2015] [Accepted: 12/22/2015] [Indexed: 11/17/2022] Open
Abstract
Wailupemycins H (1) and I (2) with a new skeleton coupled two 6-(2-phenylnaphthalene-1-yl)pyrane-2-one nuclei to a –CH2– linkage were identified from the culture of Streptomyces sp. OUCMDZ-3434 associated with the marine algae, Enteromorpha prolifera. Compounds 1 and 2 are two new α-glucosidase inhibitors with the Ki/IC50 values of 16.8/19.7 and 6.0/8.3 μM, respectively. In addition, the absolute configurations of wailupemycins D (3) and E (4) are also resolved in this paper for the first time.
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Affiliation(s)
- Zhengbo Chen
- Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
| | - Jiejie Hao
- Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
| | - Liping Wang
- Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China
| | - Yi Wang
- Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
| | - Fandong Kong
- Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
| | - Weiming Zhu
- Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
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Kim J, Kim HK, Kim S, Imm JY, Whang KY. Whey Protein Concentrate Hydrolysate Prevents Bone Loss in Ovariectomized Rats. J Med Food 2015; 18:1349-56. [PMID: 26367331 PMCID: PMC4685489 DOI: 10.1089/jmf.2015.3441] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Accepted: 05/19/2015] [Indexed: 11/13/2022] Open
Abstract
Milk is known as a safe food and contains easily absorbable minerals and proteins, including whey protein, which has demonstrated antiosteoporotic effects on ovariectomized rats. This study evaluated the antiosteoporotic effect of whey protein concentrate hydrolysate (WPCH) digested with fungal protease and whey protein concentrate (WPC). Two experiments were conducted to determine (1) efficacy of WPCH and WPC and (2) dose-dependent impact of WPCH in ovariectomized rats (10 weeks old). In Experiment I, ovariectomized rats (n=45) were allotted into three dietary treatments of 10 g/kg diet of WPC, 10 g/kg diet of WPCH, and a control diet. In Experiment II, ovariectomized rats (n=60) were fed four different diets (0, 10, 20, and 40 g/kg of WPCH). In both experiments, sham-operated rats (n=15) were also fed a control diet containing the same amount of amino acids and minerals as dietary treatments. After 6 weeks, dietary WPCH prevented loss of bone, physical properties, mineral density, and mineral content, and improved breaking strength of femurs, with similar effect to WPC. The bone resorption enzyme activity (tartrate resistance acid phosphatase) in tibia epiphysis decreased in response to WPCH supplementation, while bone formation enzyme activity (alkaline phosphatase) was unaffected by ovariectomy and dietary treatment. Bone properties and strength increased as the dietary WPCH level increased (10 and 20 g/kg), but there was no difference between the 20 and 40 g/kg treatment. WPCH and WPC supplementation ameliorated bone loss induced by ovariectomy in rats.
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Affiliation(s)
- Jonggun Kim
- Division of Biotechnology, Korea University, Seoul, Korea
| | - Hyung Kwan Kim
- Division of Biotechnology, Korea University, Seoul, Korea
| | - Saehun Kim
- Division of Food Bioscience and Technology, Korea University, Seoul, Korea
| | - Ji-Young Imm
- Department of Foods and Nutrition, Kookmin University, Seoul, Korea
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Fonseca H, Moreira-Gonçalves D, Amado F, Esteves JL, Duarte JA. Skeletal deterioration following ovarian failure: can some features be a direct consequence of estrogen loss while others are more related to physical inactivity? J Bone Miner Metab 2015; 33:605-14. [PMID: 25298329 DOI: 10.1007/s00774-014-0626-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2014] [Accepted: 08/05/2014] [Indexed: 11/26/2022]
Abstract
Findings on experimental animals show that ovarian failure is accompanied by a decrease in motor activity. As mechanical loading has a vital role in the maintenance of skeletal health, our aim was to determine to what extent this decrease in motor activity contributes to ovariectomy-induced bone loss. Thirty-two female Wistar rats were ovariectomized or sham-operated and housed in standard cages or with access to running wheels for 36 weeks with their running distance monitored. Markers of bone turnover were assayed in the serum, and bone geometry, trabecular and cortical bone microarchitecture, mineralization degree, and biomechanical properties were assessed in the femur. Differences between groups were determined by one-way ANOVA. Although reduced motor activity and sex steroid deficiency both resulted in decreases in trabecular bone volume, trabecular number decreases were mostly associated with sex steroid deficiency, whereas trabecular thickness decreases were mostly associated with sedentary behavior. Cortical bone appeared to be more sensitive to variations in motor activity, whereas bone turnover rate and bone tissue mineralization degree seemed to be primarily affected by sex steroid deficiency, even though they were further aggravated by sedentary behavior. Increases in femur length were mostly a consequence of sex steroid deficiency, whereas femoral neck length was also influenced by sedentary behavior. Differences in mechanical properties resulted mostly from differences in physical activity. Both the direct effect of sex steroid deficiency and the indirect effect of motor activity changes are implicated in bone loss following ovariectomy.
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Affiliation(s)
- Hélder Fonseca
- CIAFEL, Faculty of Sport, University of Porto, Rua Dr. Plácido Costa 91, 4200-450, Porto, Portugal.
| | - Daniel Moreira-Gonçalves
- CIAFEL, Faculty of Sport, University of Porto, Rua Dr. Plácido Costa 91, 4200-450, Porto, Portugal
| | - Francisco Amado
- Escola Superior de Saude, Universidade de Aveiro, Aveiro, Portugal
| | - José L Esteves
- INEGI, Faculty of Engineering, University of Porto, Porto, Portugal
| | - José Alberto Duarte
- CIAFEL, Faculty of Sport, University of Porto, Rua Dr. Plácido Costa 91, 4200-450, Porto, Portugal
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Fisman EZ, Tenenbaum A. Antidiabetic treatment with gliptins: focus on cardiovascular effects and outcomes. Cardiovasc Diabetol 2015; 14:129. [PMID: 26415691 PMCID: PMC4587723 DOI: 10.1186/s12933-015-0294-0] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Accepted: 09/21/2015] [Indexed: 12/11/2022] Open
Abstract
The traditional oral pharmacological therapy for type 2 diabetes mellitus (T2DM) has been based on the prescription of metformin, a biguanide, as first line antihyperglycemic agent world over. It has been demonstrated that after 3 years of treatment, approximately 50 % of diabetic patients could achieve acceptable glucose levels with monotherapy; but by 9 years this had declined to only 25 %. Therefore, the implementation of a combined pharmacological therapy acting via different pathways becomes necessary, and its combination with a compound of the sulfonylurea group was along decades the most frequently employed prescription in routine clinical practice. Meglitinides, glitazones and alpha-glucosidase inhibitors were subsequently developed, but the five mentioned groups of oral antihyperglycemic agents are associated with variable degrees of undesirable or even severe cardiovascular events. The gliptins—also called dipeptidyl peptidase 4 (DPP4) inhibitors—are an additional group of antidiabetic compounds with increasing clinical use. We review the status of the gliptins with emphasis on their capabilities to positively or negatively affect the cardiovascular system, and their potential involvement in major adverse cardiovascular events (MACE). Alogliptin, anagliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin and vildagliptin are the compounds currently in clinical use. Regardless differences in chemical structure and metabolic pathways, gliptins as a group exert favorable changes in experimental models. These changes, as an almost general rule, include improved endothelial function, reduction of inflammatory markers, oxidative stress ischemia/reperfusion injury and atherogenesis. In addition, increased adiponectin levels and modest decreases in lipidemia and blood pressure were reported. In clinical settings, several trials—notably the longer one, employing sitagliptin, with a mean follow-up period of 3 years—did not show an increased risk for ischemic events. Anyway, it should be emphasized that the encouraging results from basic science were not yet translated into clinical evidence, probably due the multiple and pleiotropic enzymatic effects of DPP4 inhibition. Moreover, when employing saxagliptin, while the drug was not associated with an augmented risk for ischemic events, it should be pinpointed that the rate of hospitalization for heart failure was significantly increased. Gliptins as a group constitute a widely accepted therapy for the management of T2DM, usually as a second-line medication. Nonetheless, for the time being, a definite relationship between gliptins treatment and improved cardiovascular outcomes remains uncertain and needs yet to be proven.
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Affiliation(s)
- Enrique Z Fisman
- Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 69978, Tel Aviv, Israel. .,Cardiovascular Diabetology Research Foundation, 58484, Holon, Israel.
| | - Alexander Tenenbaum
- Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 69978, Tel Aviv, Israel. .,Cardiovascular Diabetology Research Foundation, 58484, Holon, Israel. .,Cardiac Rehabilitation Institute, Sheba Medical Center, 52621, Tel Hashomer, Israel.
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Cawsey S, Padwal R, Sharma AM, Wang X, Li S, Siminoski K. Women with severe obesity and relatively low bone mineral density have increased fracture risk. Osteoporos Int 2015; 26:103-11. [PMID: 25182230 DOI: 10.1007/s00198-014-2833-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2013] [Accepted: 07/29/2014] [Indexed: 12/29/2022]
Abstract
UNLABELLED Among women with obesity, those with the lowest bone density have the highest fracture risk. The types of fractures include any fracture, fragility-type fractures (vertebra, hip, upper arm, forearm, and lower leg), hand and foot fractures, osteoporotic, and other fracture types. INTRODUCTION Recent reports have contradicted the traditional view that obesity is protective against fracture. In this study, we have evaluated the relationship between fracture history and bone mineral density (BMD) in subjects with obesity. METHODS Fracture risk was assessed in 400 obese women in relation to body mass index (BMI), BMD, and clinical and laboratory variables. RESULTS Subjects (mean age, 43.8 years; SD, 11.1 years) had a mean BMI of 46.0 kg/m(2) (SD, 7.4 kg/m(2)). There were a total of 178 self-reported fractures in 87 individuals (21.8% of subjects); fragility-type fractures (hip, vertebra, proximal humerus, distal forearm, and ankle/lower leg) were present in 58 (14.5%). There were higher proportions of women in the lowest femoral neck BMD quintile who had any fracture history (41.3 vs. 17.2%, p < 0.0001), any fragility-type fractures (26.7 vs. 11.7%, p = 0.0009), hand and foot fractures (16.0 vs. 5.5%, p = 0.002), other fracture types (5.3 vs. 1.2%, p = 0.02), and osteoporotic fractures (8.0 vs. 1.2%, p < 0.0001) compared to the remaining population. The odds ratio for any fracture was 0.63 (95% CI, 0.49-0.89; p = 0.0003) per SD increase in BMD and was 4.3 (95% CI, 1.9-9.4; p = 0.003) in the lowest BMD quintile compared to the highest quintile. No clinical or biochemical predictors of fracture risk were identified apart from BMD. CONCLUSIONS Women with obesity who have the lowest BMD values, despite these being almost normal, have an elevated risk of fracture compared to those with higher BMD.
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Affiliation(s)
- S Cawsey
- Division of Endocrinology and Metabolism, Department of Medicine, University of Alberta, 362 Heritage Medical Building, Edmonton, AB, Canada, T6G 2S2,
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Papaetis GS. Incretin-based therapies in prediabetes: Current evidence and future perspectives. World J Diabetes 2014; 5:817-834. [PMID: 25512784 PMCID: PMC4265868 DOI: 10.4239/wjd.v5.i6.817] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2014] [Revised: 09/10/2014] [Accepted: 11/10/2014] [Indexed: 02/05/2023] Open
Abstract
The prevalence of type 2 diabetes (T2D) is evolving globally at an alarming rate. Prediabetes is an intermediate state of glucose metabolism that exists between normal glucose tolerance (NGT) and the clinical entity of T2D. Relentless β-cell decline and failure is responsible for the progression from NGT to prediabetes and eventually T2D. The huge burden resulting from the complications of T2D created the need of therapeutic strategies in an effort to prevent or delay its development. The beneficial effects of incretin-based therapies, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, on β-cell function in patients with T2D, together with their strictly glucose-depended mechanism of action, suggested their possible use in individuals with prediabetes when greater β-cell mass and function are preserved and the possibility of β-cell salvage is higher. The present paper summarizes the main molecular intracellular mechanisms through which GLP-1 exerts its activity on β-cells. It also explores the current evidence of incretin based therapies when administered in a prediabetic state, both in animal models and in humans. Finally it discusses the safety of incretin-based therapies as well as their possible role in order to delay or prevent T2D.
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Zambrano MB, Brizola ES, Refosco L, Giugliani R, Félix TM. Anthropometry, Nutritional Status, and Dietary Intake in Pediatric Patients with Osteogenesis Imperfecta. J Am Coll Nutr 2014; 33:18-25. [DOI: 10.1080/07315724.2013.827065] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Yoshioka K. Efficacy of initial Basal-supported oral therapy with sitagliptin in untreated type 2 diabetes. Diabetes Ther 2013; 4:409-16. [PMID: 24127136 PMCID: PMC3889313 DOI: 10.1007/s13300-013-0043-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2013] [Indexed: 10/26/2022] Open
Abstract
INTRODUCTION The present study assessed the efficacy of initial basal-supported oral therapy (BOT) with sitagliptin for achievement of glycemic control and subsequent switching from BOT to sitagliptin-based oral therapy. METHODS Nineteen recently diagnosed type 2 diabetic patients who had received no antidiabetic medication in the previous 2 years were sequentially examined for the 24-week study. Patients were initially treated with a combination of insulin glargine and sitagliptin. Sitagliptin was initiated and maintained at a dose of 50 mg/day, and insulin glargine was started at a dose of 4 U at bedtime and adjusted if needed. RESULTS During the 24-week treatment period, 12 patients (63%) achieved HbA1c levels <7% (mean BOT duration 13.7 ± 5.6 weeks) and switched from BOT to sitagliptin monotherapy or in combination with metformin (achievers). The remaining seven patients (37%) failed to achieve HbA1c levels <7% (non-achievers) and continued on BOT. Both FPG and HbA1c in achievers significantly dropped at 4, 8, 12 and 24 weeks from baseline, while those in non-achievers significantly decreased at 12 and 24 weeks from baseline, but failed to reach target glycemic control. There were statistically significant differences in FPG at 4, 8, 12 and 24 weeks and in HbA1c at 8, 12 and 24 weeks between achievers and non-achievers. Body weight and BMI in achievers were significantly reduced at 12 and 24 weeks, but those in non-achievers did not change significantly. Dosage of concomitant insulin during BOT was significantly lower in achievers compared to non-achievers. Non-achievers had a similar CPI, a measure of insulin secretion capacity, to achievers, but significantly showed an insulin resistance index (value of 20/[fasting CPR × FPG]), in comparison to achievers. CONCLUSION Initiating BOT with sitagliptin followed by sitagliptin-based oral therapy is a useful option in untreated and poorly controlled patients with type 2 diabetes.
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Affiliation(s)
- Keiji Yoshioka
- Yoshioka Diabetes Clinic, 4F, The Tower, Bunroku Hills, Moriguchi Midsite, 11-2, Moriguchi, Osaka, 570-0028, Japan,
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Amstrup AK, Sikjaer T, Mosekilde L, Rejnmark L. Melatonin and the skeleton. Osteoporos Int 2013; 24:2919-27. [PMID: 23716040 DOI: 10.1007/s00198-013-2404-8] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Accepted: 05/15/2013] [Indexed: 12/15/2022]
Abstract
Melatonin may affect bone metabolism through bone anabolic as well as antiresorptive effects. An age-related decrease in peak melatonin levels at nighttime is well documented, which may increase bone resorption and bone loss in the elderly. In vitro, melatonin reduces oxidative stress on bone cells by acting as an antioxidant. Furthermore, melatonin improves bone formation by promoting differentiation of human mesenchymal stem cell (hMSC) into the osteoblastic cell linage. Bone resorption is reduced by increased synthesis of osteoprogeterin (OPG), a decoy receptor that prevents receptor activator of NK-κB ligand (RANKL) in binding to its receptor. Moreover, melatonin is believed to reduce the synthesis of RANKL preventing further bone resorption. In ovariectomized as well as nonovariectomized rodents, melatonin has shown beneficial effects on bone as assessed by biochemical bone turnover markers, DXA, and μCT scans. Furthermore, in pinealectomized animals, bone mineral density (BMD) is significantly decreased compared to controls, supporting the importance of sufficient melatonin levels. In humans, dysfunction of the melatonin signaling pathway may be involved in idiopathic scoliosis, and the increased fracture risk in nighttime workers may be related to changes in the circadian rhythm of melatonin. In the so-far only randomized study on melatonin treatment, no effects were, however, found on bone turnover markers. In conclusion, melatonin may have beneficial effects on the skeleton, but more studies on humans are warranted in order to find out whether supplementation with melatonin at bedtime may preserve bone mass and improve bone biomechanical competence.
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Affiliation(s)
- A K Amstrup
- Department of Internal Medicine and Endocrinology (MEA), THG Tage-Hansens Gade 2, Aarhus University Hospital, 8000 Aarhus, Denmark,
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Kim JY, Chae SU, Kim GD, Cha MS. Changes of paraspinal muscles in postmenopausal osteoporotic spinal compression fractures: magnetic resonance imaging study. J Bone Metab 2013; 20:75-81. [PMID: 24524061 PMCID: PMC3910309 DOI: 10.11005/jbm.2013.20.2.75] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2013] [Revised: 10/06/2013] [Accepted: 10/07/2013] [Indexed: 01/10/2023] Open
Abstract
Background To investigate the changes of cross sectional area (CSA) in paraspinal muscles upon magnetic resonance imaging (MRI) and bone mineral density (BMD) in postmenopausal osteoporotic spinal compression fractures. Methods We reviewed 81 postmenopausal women with osteoporosis, who had underwent MRI examination. The patients were divided into 51 patients who had osteoporotic spinal compression fractures (group I), and 30 patients who without fractures (group II). Group I were subdivided into IA and IB, based on whether they were younger (IA) of older (IB) than 70 years of age. We additionally measured body mass index and BMD. The CSA of multifidus, erector spinae, paraspinal muscles, psoas major (PT), and intervertebral (IV) discs were measured. The degree of fatty atrophy was estimated using three grades. Results The BMD and T-score of group I were significantly lower than those of group II. The CSA of erector spinae, paraspinal muscles, and PT in the group I was significantly smaller than that of group II. The CSA of paraspinal muscles in group IB were significantly smaller than those of group IA. The CSA of erector spinae, mutifidus, and PT in group IB were smaller than those of group IA, but the difference was not statistically significant. Group 1 exhibited greater fat infiltration in the paraspinal muscle than group II. Conclusions Postmenopausal osteoporotic spinal compression fracture is associated with profound changes of the lumbar paraspinal muscle, reduction of CSA, increased CSA of IV disc, and increased intramuscular fat infiltration.
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Affiliation(s)
- Jong Yun Kim
- Department of Orthopedic Surgery, School of Medicine, Wonkwang University Hospital, Iksan, Korea
| | - Soo Uk Chae
- Department of Orthopedic Surgery, School of Medicine, Wonkwang University Hospital, Iksan, Korea
| | - Gang Deuk Kim
- Department of Radiology, School of Medicine, Wonkwang University Hospital, Iksan, Korea
| | - Myoung Soo Cha
- Department of Orthopedic Surgery, School of Medicine, Wonkwang University Hospital, Iksan, Korea
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Zhu J, Huang X, Gao H, Bao Q, Zhao Y, Hu JF, Xia G. A novel glucagon-like peptide 1 peptide identified from Ophisaurus harti. J Pept Sci 2013; 19:598-605. [PMID: 23893560 DOI: 10.1002/psc.2538] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2013] [Revised: 06/18/2013] [Accepted: 06/18/2013] [Indexed: 11/06/2022]
Abstract
Glucagon-like peptide 1 receptor (GLP1R) is a promising target for the treatment of type 2 diabetes. Because of the short half-life of endogenous GLP1 peptide, other GLP1R agonists are considered to be appealing therapeutic candidates. A high-throughput assay has been established to screen for GLP1R agonists in a 60 000-well natural product compound library fractionated from 670 different herbs/materials widely used in traditional Chinese medicines (TCMs). The screening is based on primary screen of GLP1R⁺ reporter gene assay with the counter screen in GLP1R⁻ cell line. An active fraction, A089-147, was identified from the screening. Fraction A089-147 was isolated from dried Ophisaurus harti, and the fact that its GLP1R agonist activity was sensitive to trypsin treatment indicates its peptidic nature. The active ingredient of A089-147 was later identified as O. harti GLP1 through transcriptome analysis. Chemically synthesized O. harti GLP1 showed GLP1R agonist activity and sensitivity to dipeptidase IV digestion. This study illustrated a comprehensive screening strategy to identify novel GLP1R agonists from TCMs libraries and at the same time underlined the difficulty of identifying a non-peptidic GLP1R agonist. The novel O. harti GLP1 peptide yielded from this study confirmed broader application of TCMs libraries in active peptide identification.
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Affiliation(s)
- Jingjing Zhu
- Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 N. Zhongshan Road, Shanghai 200062, China
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Gautier-Stein A, Mithieux G. A role for PYY3-36 in GLP1-induced insulin secretion. Mol Metab 2013; 2:123-5. [PMID: 24049724 DOI: 10.1016/j.molmet.2013.06.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2013] [Accepted: 06/04/2013] [Indexed: 10/26/2022] Open
Affiliation(s)
- Amandine Gautier-Stein
- Inserm U855, Lyon, France ; Université Lyon 1, Villeurbanne, France ; Université de Lyon, Lyon, France
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Yoshioka K, Isotani H, Ohashi SI, Imamura M. Efficacy of vildagliptin on glucose fluctuation in Japanese type 2 diabetic patients with ongoing sulfonylurea based oral glycemic agent therapy. Diabetes Metab Syndr 2013; 7:32-34. [PMID: 23517793 DOI: 10.1016/j.dsx.2013.02.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
AIM To investigate whether vildagliptin, one of the dipeptidylpeptide-4 (DDP-4) inhibitors, improves not only glycemic control but also glycemic fluctuation when added to ongoing sulfonylurea (SU) based oral hypoglycemic agents (OHA) therapy in patients with type 2 diabetes mellitus (T2DM). METHODS A total of 19 patients with T2DM were recruited from outpatients. Vildagliptin was initiated with a dose of 100mg per day in the patients who had inadequate glycemic control and glycemic fluctuation with ongoing SU based OHA therapy. Glycemic excursion was defined by seven-point self-monitoring blood glucose (SMBG) on three days at baseline and 12 weeks after vildagliptin-combined therapy, as well as HbA1c levels. M-value and J-index were calculated to evaluate glycemic excursion. RESULTS Addition of vildagliptin to ongoing SU based OHA therapy significantly decreased HbA1c values from 8.2 ± 3.8% at baseline to 7.3 ± 0.8% at 12-week. The average of blood glucose profiles was significant improved. As a result, M-value was significantly corrected from 20.9 ± 14.4 to 12.2 ± 13.5 and J-index from 55.1 ± 25.5 to 39.1 ± 19.8. CONCLUSIONS Vildagliptin when added to ongoing SU based OHA therapy for 12 weeks significantly improved glycemic fluctuation as well as glycemic control in Japanese patients with T2DM.
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Sanada K, Iemitsu M, Murakami H, Gando Y, Kawano H, Kawakami R, Tabata I, Miyachi M. Adverse effects of coexistence of sarcopenia and metabolic syndrome in Japanese women. Eur J Clin Nutr 2012; 66:1093-8. [PMID: 22569087 DOI: 10.1038/ejcn.2012.43] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND/OBJECTIVES Little information is available regarding the interactions of sarcopenia and metabolic syndrome (MetS) in the risks of these age-associated diseases in women. The present cross-sectional study was performed to investigate whether the coexistence of sarcopenia and MetS further increases the risks of lifestyle-related diseases in Japanese women. SUBJECTS/METHODS Healthy Japanese women (n=533) aged 30-84 participated in this study. MetS was defined as higher body mass index, fasting plasma glucose, systolic or diastolic blood pressure and blood lipid abnormalities. Appendicular muscle mass and bone mineral density (BMD) were measured using dual-energy X-ray absorptiometry. The criterion of low muscle mass and strength defined median skeletal muscle index (appendicular muscle mass/height², kg/m²) and handgrip strength. RESULTS Two-way ANCOVA with adjustment for age, body fat percentage and whole-body lean tissue mass indicated that sarcopenia and MetS interacted to produce a significant effect on HbA1c, systolic blood pressure, triglycerides and brachial-ankle pulse wave velocity in Japanese women. The systolic blood pressure, triglycerides and brachial-ankle pulse wave velocity were significantly higher in women with coexisting sarcopenia and MetS than in healthy controls or in those with sarcopenia or MetS alone. The HbA1c in the coexisting sarcopenia and MetS group was higher than in healthy controls and sarcopenia subjects. CONCLUSIONS The coexistence of sarcopenia and MetS further increases the risks of cardiovascular diseases, such as type 2 diabetes mellitus, hypertension, arterial stiffness and hyperlipidemia even adjustment of age and body composition in adult Japanese women.
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Affiliation(s)
- K Sanada
- Faculty of Sport and Health Science, Ritsumeikan University, Shiga, Japan.
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Abstract
Liraglutide is a United States Food and Drug Administration (FDA)-approved glucagon-like peptide-1 (GLP-1) analog that is 97% homologous to native human GLP-1. The additional 16-carbon fatty acid chain causes noncovalent binding to albumin, which slows absorption from the injection site and protects the molecule from degradation by the enzyme dipeptidyl peptidase-4, allowing for protraction of action. Albumin binding and an elimination half-life of 13 hours combine to allow for once-daily dosing. Liraglutide 1.2 and 1.8 mg/day given as monotherapy for up to 52 weeks produced mean reductions in hemoglobin A1c (A1C) of 0.6-1.6%; combination therapy of liraglutide with oral antidiabetic agents demonstrated mean A1C reductions up to 1.5%. The satiety effect of GLP-1 receptor agonists and documented weight loss as great as 3.38 kg in clinical trials may make liraglutide ideal for obese patients with type 2 diabetes mellitus. Like other incretin-based agents, preliminary studies suggest liraglutide may also increase β-cell mass and function. Hypoglycemia is rare with liraglutide and tends to occur when used in combination with sulfonylureas; liraglutide in combination with insulin is not yet FDA approved. The pharmacokinetic parameters of liraglutide are unaffected by age, sex, race, or ethnicity, and no special recommendations for altered dosing of liraglutide need apply to populations with hepatic or renal impairment. Results from clinical trials have not shown an increased risk of medullary thyroid cancer, pancreatitis, or poor cardiovascular outcomes with liraglutide treatment. Ongoing, long-term monitoring studies continue to evaluate the safety of liraglutide treatment in these outcomes.
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Affiliation(s)
- Evan M Sisson
- 1 Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia 23298-0533, USA.
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Renvert S, Berglund J, Persson RE, Persson GR. Osteoporosis and periodontitis in older subjects participating in the Swedish National Survey on Aging and Care (SNAC-Blekinge). Acta Odontol Scand 2011; 69:201-7. [PMID: 21254955 DOI: 10.3109/00016357.2010.549501] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Abstract Objective. We assessed the relationships between (I) ultrasonography calcaneus T-scores (PIXI) and mandibular cortex characteristics on oral panoramic radiographs in older subjects; and (II) osteoporosis and periodontitis. Material and methods. We examined 778 subjects (53% women) aged 59-96 years. Periodontitis was defined by alveolar bone loss assessed from panoramic radiographs. Results. PIXI calcaneus T-values ≤-2.5 (osteoporosis) were found in 16.3% of women and in 8.1% of men. PIXI calcaneus T-values <-1.6 (osteoporosis, adjusted) were found in 34.2% of women and in 21.4% of men. The age of the subjects and PIXI T-values were significantly correlated in women (Pearson's r = 0.37, P < 0.001) and men (Pearson's r = 0.19, P < 0.001). Periodontitis was found in 18.7% of subjects defined by alveolar bone level ≥5 mm. Subjects with osteoporosis defined by adjusted PIXI T-values had fewer remaining teeth [mean difference 4.1, 95% confidence interval (CI) -1.1 to -6.5, P < 0.001]. The crude odds ratio (OR) of an association between the panoramic assessment of mandibular cortex erosions as a sign of osteoporosis and the adjusted T-value (T-value cut-off <-1.6) was 4.8 (95% CI 3.1-7.2, P < 0.001; Pearson χ(2) = 60.1, P < 0.001). A significant OR between osteoporosis and periodontitis was only found in women for the T-value cut-off ≤-2.5 (crude OR 1.8, 95% CI 1.1-3.3, P < 0.03). Conclusions. An association between osteoporosis and periodontitis was only confirmed in women. The likelihood that the mandibular cortex index agrees with adjusted PIXI T-values is significant.
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Affiliation(s)
- Stefan Renvert
- Department of Oral Sciences , School of Health and Society, Kristianstad University, Sweden.
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Brindis F, Rodríguez R, Bye R, González-Andrade M, Mata R. (Z)-3-butylidenephthalide from Ligusticum porteri , an α-glucosidase inhibitor. JOURNAL OF NATURAL PRODUCTS 2011; 74:314-320. [PMID: 20879744 DOI: 10.1021/np100447a] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2023]
Abstract
An extract from the roots of Ligusticum porteri, orally administered to groups of normal and diabetic mice, showed significant hypoglycemic and antihyperglycemic effects. Experimental type-II DM was achieved by treating mice with streptozotocin 15 min after an injection of β-nicotinamide adenine dinucleotide. (Z)-6,6',7,3'α-diligustilide (1), (Z)-ligustilide (2), 3-(Z)-butylidenephthalide (3), myristicin (4), and ferulic acid (5) were isolated from the active extract. When tested In Vivo, compounds 1-3 showed antihyperglycemic activity, with 3 being the most active. Compound 3 (56.2 mg/kg) decreased blood glucose levels in NAD-STZ-diabetic mice after an oral sucrose load, suggesting that its antihyperglycemic effect is due to inhibition of α-glucosidase at the intestinal level. Furthermore, 3 inhibited the activity of yeast-α-glucosidase (IC(50) 2.35 mM) in a noncompetitive fashion with a K(i) of 4.86 mM. Docking analysis predicted that 3 binds to the enzyme in a pocket close to the catalytic site, but different from that for acarbose, with a K(i) of 11.48 mM. Compounds 1 and 2 did not affect α-glucosidase In Vivo, but altered glucose absorption by a mechanism yet to be determined. The stimulatory effect of 5 on insulin secretion, present in high amounts in the extract, has been demonstrated in previous investigations. The present study provides scientific support of the use of L. porteri in Mexican folk medicine for the treatment of diabetes.
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Affiliation(s)
- Fernando Brindis
- Facultad de Química, Universidad Nacional Autónoma de México, México DF 04510, México
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Sakai A, Oshige T, Zenke Y, Yamanaka Y, Otsuka H, Nakamura T. Shorter unipedal standing time and lower bone mineral density in women with distal radius fractures. Osteoporos Int 2010; 21:733-9. [PMID: 19543845 DOI: 10.1007/s00198-009-0992-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2009] [Accepted: 06/01/2009] [Indexed: 10/20/2022]
Abstract
UNLABELLED Unipedal standing time was shorter and bone mineral density was lower in Japanese women aged 50 years and over with low-energy distal radius fractures resulting from falls than those in age-matched community-dwelling Japanese women without distal radius fractures. INTRODUCTION The aim of this study was to compare unipedal standing time and bone mineral density (BMD) of women >or=50 years of age with distal radius fractures with those of age-matched women without fractures. METHODS Fracture group was 54 Japanese women with low-energy distal radius fractures resulting from fall. Non-fracture group was 52 community-dwelling Japanese women without fractures. Unipedal standing time and BMD were measured. RESULTS There were no significant differences in age and body mass index between the two groups. The percentage of women with unipedal standing time <15 s was 44.4% in the fracture group and 13.5% in the non-fracture group, while the respective frequencies for >120 s were 20.4% and 50.0%. The T-score of BMD was significantly lower in the fracture than non-fracture group. Logistic regression analysis identified unipedal standing time <15 s and T-score <70% as significant factors associated with distal radius fractures. Notably, T-score <70% was significant in subjects <65 years, and unipedal standing time <15 s was significant in those >or=65 years. CONCLUSION Unipedal standing time was shorter and BMD was lower in women >or=50 years of age with distal radius fractures than those in age-matched women without fractures.
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Affiliation(s)
- A Sakai
- Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan.
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Pirro M, Fabbriciani G, Leli C, Callarelli L, Manfredelli MR, Fioroni C, Mannarino MR, Scarponi AM, Mannarino E. High weight or body mass index increase the risk of vertebral fractures in postmenopausal osteoporotic women. J Bone Miner Metab 2010; 28:88-93. [PMID: 19578807 DOI: 10.1007/s00774-009-0108-0] [Citation(s) in RCA: 83] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2009] [Accepted: 06/03/2009] [Indexed: 10/20/2022]
Abstract
In the general population, low body weight and body mass index (BMI) are significant risk factors for any fracture, but the specific association between body weight, BMI, and prevalence of vertebral fractures in osteoporotic women is not fully recognized. Hence, the association between body weight, BMI, and prevalent vertebral fractures was investigated in 362 women with never-treated postmenopausal osteoporosis. All participants underwent measurement of BMI, bone mineral density (BMD), and semiquantitative assessment of vertebral fractures. Thirty percent of participants had > or =1 vertebral fracture. Body weight and BMI were associated with L1-L4 BMD (R = 0.29, P < 0.001 and R = 0.17, P = 0.009, respectively). In logistic regression analysis, BMI was positively associated with the presence of vertebral fractures independent of age and other traditional risk factors for fractures. Including weight and height instead of BMI in the multivariate model, showed weight as a positive and significant covariate of the presence of vertebral fractures (OR = 1.045; P = 0.016; 95% CI 1.008-1.084). BMI was associated with the number of vertebral fractures (rho = 0.18; P = 0.001), this association being confirmed also in the multivariate analysis (beta = 0.14; P = 0.03) after correction for smoking, early menopause, family history of fragility fractures and BMD. In conclusion, among postmenopausal women with osteoporosis, body weight and BMI are associated with a higher likelihood of having a vertebral fracture, irrespective of the positive association between weight and BMD.
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Affiliation(s)
- Matteo Pirro
- Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Clinical and Experimental Medicine, University of Perugia, Hospital "Santa Maria della Misericordia", Piazzale Menghini 1, 06129 Perugia, Italy.
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42
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Morin S, Leslie WD. High bone mineral density is associated with high body mass index. Osteoporos Int 2009; 20:1267-71. [PMID: 19034375 DOI: 10.1007/s00198-008-0797-6] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2008] [Accepted: 09/19/2008] [Indexed: 10/21/2022]
Abstract
SUMMARY High BMD is an infrequent finding. In this retrospective cohort study of women 50 years and older, we documented a strong association between high BMD and high BMI. INTRODUCTION High bone mineral density (BMD) has been associated with genetic disorders and a variety of dietary, endocrine, metabolic, infectious and neoplastic diseases that in many cases warrant medical attention. Since body mass index (BMI) is closely correlated with BMD, we sought to explore the relationship between these two parameters in older women. METHODS We conducted a retrospective clinical cohort study of 16,500 women 50 years and older who underwent baseline BMD testing between May 1998 and October 2002. Mean T-scores and Z-scores, and the proportions of women with high BMD (T-score +2.5 or greater, Z-score +2.0 or greater), were assessed according to BMI category. RESULTS Higher BMI category was associated with higher mean T-scores and Z-scores at all sites (P < 0.001). The proportion of women with high BMD increased with each BMI category (P for trend <0.05). In women with a lumbar spine T-score of +2.5 or more, 43.5% were obese with BMI > 30 kg/m(2) (55.6% for the femoral neck and 73.1% for the total hip). For women with a lumbar spine Z-score of +2.0 or more, 37.2% were obese (42.0% for the femoral neck and 50.9% for the total hip). There was no evidence of a paradoxical increase in fracture rates in women with high BMD. CONCLUSIONS High BMD is closely associated with elevated BMI in women. This should be taken into consideration prior to initiating extensive investigations for rare pathologies.
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Affiliation(s)
- S Morin
- Department of Medicine, McGill University, Montreal, Canada.
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Sakai A, Toba N, Takeda M, Suzuki M, Abe Y, Aoyagi K, Nakamura T. Association of unipedal standing time and bone mineral density in community-dwelling Japanese women. Osteoporos Int 2009; 20:731-6. [PMID: 18763011 DOI: 10.1007/s00198-008-0726-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2008] [Accepted: 07/21/2008] [Indexed: 11/28/2022]
Abstract
UNLABELLED Bone mineral density (BMD) and physical performance of the lower extremities decrease with age. In community-dwelling Japanese women, unipedal standing time, timed up and go test, and age are associated with BMD while in women aged 70 years and over, unipedal standing time is associated with BMD. INTRODUCTION The aim of this study was to clarify whether unipedal standing time is significantly associated with BMD in community-dwelling women. METHODS The subjects were 90 community-dwelling Japanese women aged 54.7 years. BMD of the second metacarpal bone was measured by computed X-ray densitometry. We measured unipedal standing time as well as timed up and go test to assess physical performance of the lower extremities. RESULTS Unipedal standing time decreased with increased age. Timed up and go test significantly correlated with age. Low BMD was significantly associated with old age, short unipedal standing time, and long timed up and go test. Stepwise regression analysis revealed that age, unipedal standing time, and timed up and go test were significant factors associated with BMD. In 21 participants aged 70 years and over, body weight and unipedal standing time, but not age, were significantly associated with BMD. CONCLUSION BMD and physical performance of the lower extremities decrease with older age. Unipedal standing time, timed up and go test, and age are associated with BMD in community-dwelling Japanese women. In women aged 70 years and over, unipedal standing time is significantly associated with BMD.
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Affiliation(s)
- A Sakai
- Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan.
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