|
1
|
Therapeutic or lifelong training effects on pancreatic morphological and functional parameters in an animal model of aging and obesity. Exp Gerontol 2023; 175:112144. [PMID: 36907475 DOI: 10.1016/j.exger.2023.112144] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 03/02/2023] [Accepted: 03/09/2023] [Indexed: 03/14/2023]
Abstract
AIMS Obesity, aging, and physical training are factors influencing pancreatic functional and morphological parameters. Aiming to clarify the impact of the interaction of these factors, we analyzed the effect of therapeutic or lifelong physical training on body adiposity and pancreatic functional and morphological parameters of aged and obese rats. METHODS 24 male Wistar rats were (initial age = 4 months and final age = 14 months) randomly divided into three aged and obese experimental groups (n = 8/group): untrained, therapeutic trained, and lifelong trained. Body adiposity, plasmatic concentration and pancreatic immunostaining of insulin, markers of tissue inflammation, lipid peroxidation, activity and immunostaining of antioxidant enzymes, and parameters of pancreatic morphology were evaluated. RESULTS Lifelong physical training improved the body adiposity, plasmatic insulin concentration, and macrophage immunostaining in the pancreas. The animals submitted to therapeutic and lifelong training showed an increase in the density of the pancreatic islets; lower insulin, Nuclear Factor Kappa B (NF-κB), and Transforming Growth Factor beta (TGF-β) immunostaining in the pancreatic parenchyma, as well as lower pancreatic tissue lipid peroxidation, lower fibrosis area, increased catalase and glutathione peroxidase (GPx) activity and increased heme oxygenase-1 (HO-1) immunostaining, with the greatest effect in the lifelong training group. CONCLUSION Lifelong training promoted greater beneficial effects on the pancreatic functional and morphological parameters of aged and obese animals compared to therapeutic exercise.
Collapse
|
|
2
|
Wen Y, Chen C, Kong X, Xia Z, Kong W, Si K, Han P, Vivian Liu W, Li X. Pancreatic fat infiltration, β-cell function and insulin resistance: A study of the young patients with obesity. Diabetes Res Clin Pract 2022; 187:109860. [PMID: 35367311 DOI: 10.1016/j.diabres.2022.109860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 03/07/2022] [Accepted: 03/29/2022] [Indexed: 11/25/2022]
Abstract
OBJECTIVE This study aimed to investigate the relationship between pancreatic fat infiltration (PFI) and glucose metabolism disorder, β-cell function and insulin resistance in patients with obesity. METHODS Pancreatic fat fraction (PFF) was quantified by MRI IDEAL-IQ technique. PFF greater than 6.2 % was defined as PFI, and 34 obese patients were divided into PFI and non-PFI groups. The 5-point plasma glucose and insulin values during oral glucose tolerance test (OGTT) were recorded. OGTT-derived indices of insulin resistance and β-cell function were calculated. RESULTS Glucose values levels at 0-120 min during OGTT were significantly higher and β-cell function variables were lower in PFI group than non-PFI group. While indices of insulin resistance were not significantly different between two groups. Correlation analysis showed that PFF was positively correlated with glucose levels at 0, 30 and 60 min, negatively correlated with β-cell function variables and not significantly correlated with indices of insulin resistance. However, these associations of PFF with β-cell function and glucose levels were only present in type 2 diabetes mellitus (T2DM) group but not in non-T2DM group. CONCLUSION There is an association between PFI and impaired β-cell function, and increased pancreatic fat may be a potential risk factor for the development of T2DM.
Collapse
Affiliation(s)
- Yu Wen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Cen Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Xiangchuang Kong
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Zefeng Xia
- Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Wen Kong
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Keke Si
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Ping Han
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | | | - Xin Li
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China.
| |
Collapse
|
|
3
|
Ko J, Skudder-Hill L, Cho J, Bharmal SH, Petrov MS. Pancreatic enzymes and abdominal adipose tissue distribution in new-onset prediabetes/diabetes after acute pancreatitis. World J Gastroenterol 2021; 27:3357-3371. [PMID: 34163117 PMCID: PMC8218354 DOI: 10.3748/wjg.v27.i23.3357] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/14/2021] [Accepted: 06/07/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND New-onset prediabetes/diabetes after acute pancreatitis (NODAP) is the most common sequela of pancreatitis, and it differs from type 2 prediabetes/diabetes mellitus (T2DM).
AIM To study the associations between circulating levels of pancreatic amylase, pancreatic lipase, chymotrypsin and fat phenotypes in NODAP, T2DM, and health.
METHODS Individuals with NODAP (n = 30), T2DM (n = 30), and sex-matched healthy individuals (n = 30) were included. Five fat phenotypes (intra-pancreatic fat, liver fat, skeletal muscle fat, visceral fat, and subcutaneous fat) were determined using the same magnetic resonance imaging protocol and scanner magnet strength for all participants. One-way analysis of covariance, linear regression analysis, and relative importance analysis were conducted.
RESULTS Intra-pancreatic fat deposition (IPFD) was higher in NODAP (9.4% ± 1.8%) and T2DM (9.8% ± 1.1%) compared with healthy controls (7.8% ± 1.9%) after adjusting for covariates (P = 0.003). Similar findings were observed in regards to visceral fat volume (P = 0.005), but not subcutaneous fat volume, liver fat, or skeletal muscle fat. Both IPFD (β = -2.201, P = 0.023) and visceral fat volume (β = -0.004, P = 0.028) were significantly associated with circulating levels of pancreatic amylase in NODAP, but not in T2DM or healthy individuals. Of the five fat phenotypes, IPFD explained the highest amount of variance in pancreatic amylase concentration (R2 = 15.3% out of 41.2%). None of the phenotypes contributed meaningfully to the variance in pancreatic lipase or chymotrypsin.
CONCLUSION Both NODAP and T2DM are characterized by increased IPFD and visceral fat volume. However, only NODAP is characterized by significant inverse associations between the two fat phenotypes and pancreatic amylase.
Collapse
Affiliation(s)
- Juyeon Ko
- School of Medicine, University of Auckland, Auckland 1142, New Zealand
| | | | - Jaelim Cho
- School of Medicine, University of Auckland, Auckland 1142, New Zealand
| | - Sakina H Bharmal
- School of Medicine, University of Auckland, Auckland 1142, New Zealand
| | - Maxim S Petrov
- School of Medicine, University of Auckland, Auckland 1142, New Zealand
| |
Collapse
|
|
4
|
Ishibashi C, Kozawa J, Hosakawa Y, Yoneda S, Kimura T, Fujita Y, Fukui K, Iwahashi H, Shimomura I. Pancreatic fat is related to the longitudinal decrease in the increment of C-peptide in glucagon stimulation test in type 2 diabetes patients. J Diabetes Investig 2020; 11:80-87. [PMID: 31240874 PMCID: PMC6944841 DOI: 10.1111/jdi.13108] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2019] [Revised: 06/11/2019] [Accepted: 06/23/2019] [Indexed: 02/06/2023] Open
Abstract
AIMS/INTRODUCTION The relationship between pancreatic fatty infiltration and diabetes is widely known, whereas the causal relationship is not clear. Furthermore, it is uncertain whether pathogenesis of pancreatic fat is similar to that of liver fat. We aimed to clarify the contribution of this type of fat to glucose metabolism in type 2 diabetes patients by cross-sectional and longitudinal analyses. MATERIAL AND METHODS A total of 56 patients with type 2 diabetes who had been hospitalized twice were analyzed. We evaluated the mean computed tomography values of the pancreas (P), liver (L) and spleen (S). Lower computed tomography values indicate a greater fat content. We defined indices of pancreatic or liver fat content as the differences between P or L and S. We assessed the associations among fat content for the two organs (P-S, L-S) and clinical parameters at the first hospitalization, and then analyzed the associations between these fat contents and changes in glycometabolic markers (the second data values minus the first). RESULTS In the cross-sectional study, P-S negatively correlated with the increment of C-peptide in the glucagon stimulation test (r = -0.71, P < 0.0001) and body mass index (r = -0.28, P = 0.034). L-S negatively correlated with homeostasis model assessment of insulin resistance (r = -0.73, P < 0.0001), body mass index (r = -0.62, P < 0.0001) and some other obesity-related indicators, but not with the increment of C-peptide in the glucagon stimulation test. In the longitudinal study, P-S positively correlated with the change of the increment of C-peptide in the glucagon stimulation test (r = 0.49, P = 0.021). CONCLUSIONS In type 2 diabetes patients, pancreatic fat was less associated with obesity-related indicators than liver fat, but was more strongly associated with the longitudinal decrease in endogenous insulin-secreting capacity.
Collapse
Affiliation(s)
- Chisaki Ishibashi
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| | - Junji Kozawa
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| | - Yoshiya Hosakawa
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| | - Sho Yoneda
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| | - Takekazu Kimura
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| | - Yukari Fujita
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
- Department of Community MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| | - Kenji Fukui
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| | - Hiromi Iwahashi
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
- Department of Diabetes Care MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| | - Iichiro Shimomura
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| |
Collapse
|
|
5
|
Chouhan MD, Firmin L, Read S, Amin Z, Taylor SA. Quantitative pancreatic MRI: a pathology-based review. Br J Radiol 2019; 92:20180941. [PMID: 30982337 DOI: 10.1259/bjr.20180941] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
MRI plays an important role in the clinical management of pancreatic disorders and interpretation is reliant on qualitative assessment of anatomy. Conventional sequences capturing pancreatic structure can however be adapted to yield quantitative measures which provide more diagnostic information, with a view to increasing diagnostic accuracy, improving patient stratification, providing robust non-invasive outcome measures for therapeutic trials and ultimately personalizing patient care. In this review, we evaluate the use of established techniques such as secretin-enhanced MR cholangiopancreatography, diffusion-weighted imaging, T 1, T 2* and fat fraction mapping, but also more experimental methods such as MR elastography and arterial spin labelling, and their application to the assessment of diffuse pancreatic disease (including chronic, acute and autoimmune pancreatitis/IgG4 disease, metabolic disease and iron deposition disorders) and cystic/solid focal pancreatic masses. Finally, we explore some of the broader challenges to their implementation and future directions in this promising area.
Collapse
Affiliation(s)
- Manil D Chouhan
- 1 University College London (UCL) Centre for Medical Imaging, Division of Medicine, UCL , London , UK.,2 Department of Imaging, University College London Hospitals (UCLH) NHS Foundation Trust , London , UK
| | - Louisa Firmin
- 2 Department of Imaging, University College London Hospitals (UCLH) NHS Foundation Trust , London , UK
| | - Samantha Read
- 2 Department of Imaging, University College London Hospitals (UCLH) NHS Foundation Trust , London , UK
| | - Zahir Amin
- 2 Department of Imaging, University College London Hospitals (UCLH) NHS Foundation Trust , London , UK
| | - Stuart A Taylor
- 1 University College London (UCL) Centre for Medical Imaging, Division of Medicine, UCL , London , UK.,2 Department of Imaging, University College London Hospitals (UCLH) NHS Foundation Trust , London , UK
| |
Collapse
|
|
6
|
Chen Y, Long L, Jiang Z, Zhang L, Zhong D, Huang X. Quantification of pancreatic proton density fat fraction in diabetic pigs using MR imaging and IDEAL-IQ sequence. BMC Med Imaging 2019; 19:38. [PMID: 31088378 PMCID: PMC6515681 DOI: 10.1186/s12880-019-0336-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Accepted: 04/25/2019] [Indexed: 12/12/2022] Open
Abstract
Background Recent studies have highlighted the correlation between diabetes and pancreatic fat infiltration. Notably, pancreatic fat content (PFC) is a potential biomarker in diabetic patients, and magnetic resonance imaging (MRI) provides an effective method for noninvasive assessment of pancreatic fat infiltration. However, most reports of quantitative measurement of pancreatic fat have lacked comparisons of pathology results. The primary objective of this study was to determine the feasibility and accuracy of pancreatic MRI by using pancreatic fat fraction (PFF) measurements with the IDEAL-IQ sequence; the secondary objective was to explore changes in PFC between pigs with and without diabetes. Methods In this prospective study, 13 Bama Mini-pigs (7 females, 6 males; median age, 2 weeks) were randomly assigned to diabetes (n = 7) or control (n = 6) groups. Pigs in the diabetes group received high fat/high sugar feed, combined with streptozotocin injections. At the end of 15 months, biochemical changes were evaluated. All pigs underwent axial MRI with the IDEAL-IQ sequence to measure PFF; PFC of fresh pancreatic parenchyma was measured by the Soxhlet extraction method; and pancreatic fat distribution was observed by histopathology. Results of all analyses were compared between the diabetes and control groups by using the Mann-Whitney U-test. Correlations of PFF and PFC, fasting blood glucose (GLU), and serum insulin (INS) were calculated by using the Spearman correlation coefficient. Single-measure intraclass correlation coefficient (ICC) was used to assess interreader agreement. Results There were significant differences between diabetes and control groups: GLU (mmol/L) was 18.06 ± 6.03 and 5.06 ± 1.41 (P < 0.001); INS (mU/L) was 21.59 ± 2.93 and 29.32 ± 3.27 (P = 0.003); PFC (%) was 34.60 ± 3.52 and 28.63 ± 3.25 (P = 0.027); and PFF (%) was 36.51 ± 4.07 and 27.75 ± 3.73 (P = 0.003). There was a strongly positive correlation between PFF and PFC (r = 0.934, P < 0.001); there were moderate correlations between PFF and GLU (r = 0.736, P = 0.004; positive correlation), and between PFF and INS (r = − 0.747, P = 0.003; negative correlation). Excellent interreader agreement was observed for PFF measurements (ICC, 0.954). Conclusions Pancreatic fat infiltration shows a clear association with diabetes. MRI with the IDEAL-IQ sequence can be used to accurately and reproducibly quantify PFC.
Collapse
Affiliation(s)
- Yidi Chen
- Radiology Department, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Liling Long
- Radiology Department, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China.
| | - Zijian Jiang
- Radiology Department, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Ling Zhang
- Radiology Department, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Delin Zhong
- Radiology Department, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Xialing Huang
- Radiology Department, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China
| |
Collapse
|
|
7
|
Chen Y, Jiang Z, Long L, Miu Y, Zhang L, Zhong D, Tang Q. Magnetic resonance imaging: Proton density fat fraction for assessment of pancreatic fatty infiltration during progression of T2DM bama minipigs. J Magn Reson Imaging 2019; 50:1905-1913. [PMID: 31006935 DOI: 10.1002/jmri.26754] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Revised: 04/03/2019] [Accepted: 04/03/2019] [Indexed: 12/15/2022] Open
Affiliation(s)
- Yidi Chen
- First Affiliated Hospital of Guangxi Medical UniversityRadiology Department Guangxi China
| | - Zijian Jiang
- First Affiliated Hospital of Guangxi Medical UniversityRadiology Department Guangxi China
| | - Liling Long
- First Affiliated Hospital of Guangxi Medical UniversityRadiology Department Guangxi China
| | - Yongjian Miu
- First Affiliated Hospital of Guangxi Medical UniversityPathology Department Guangxi China
| | - Ling Zhang
- First Affiliated Hospital of Guangxi Medical UniversityRadiology Department Guangxi China
| | - Delin Zhong
- First Affiliated Hospital of Guangxi Medical UniversityRadiology Department Guangxi China
| | - Qin Tang
- First Affiliated Hospital of Guangxi Medical UniversityRadiology Department Guangxi China
| |
Collapse
|
|
8
|
Hamaguchi T, Hirota Y, Takeuchi T, Nakagawa Y, Matsuoka A, Matsumoto M, Awano H, Iijima K, Cha PC, Satake W, Toda T, Ogawa W. Treatment of a case of severe insulin resistance as a result of a PIK3R1 mutation with a sodium-glucose cotransporter 2 inhibitor. J Diabetes Investig 2018; 9:1224-1227. [PMID: 29476696 PMCID: PMC6123033 DOI: 10.1111/jdi.12825] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Revised: 01/19/2018] [Accepted: 02/14/2018] [Indexed: 12/28/2022] Open
Abstract
A Japanese woman aged in her late 30s with severe insulin resistance and bodily features including a triangular face, prominent forehead, small chin, large and low-set ears, and ocular depression was investigated. A similar phenotype was not observed in other family members with the exception of her son, suggesting that the condition was caused by a de novo mutation that was transmitted from mother to son. Exome analysis showed the presence in the proband and her son of a c.1945C>T mutation in PIK3R1, a common mutation associated with SHORT (short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay) syndrome. Administration of a sodium-glucose cotransporter 2 inhibitor lowered the proband's hemoglobin A1c level and allowed a reduction in her insulin dose without treatment-related adverse events including ketoacidosis, exaggerated loss of body mass or hypoglycemia. Sodium-glucose cotransporter 2 inhibitors might thus offer an additional option for the treatment of genetic syndromes of severe insulin resistance.
Collapse
Affiliation(s)
| | - Yushi Hirota
- Division of Diabetes and EndocrinologyTokyoJapan
| | | | | | | | - Masaaki Matsumoto
- Department of PediatricsKobe University Graduate School of MedicineKobeJapan
| | - Hiroyuki Awano
- Department of PediatricsKobe University Graduate School of MedicineKobeJapan
| | - Kazumoto Iijima
- Department of PediatricsKobe University Graduate School of MedicineKobeJapan
| | - Pei Chieng Cha
- Division of NeurologyDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Wataru Satake
- Division of NeurologyDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Tatsushi Toda
- Division of NeurologyDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
- Department of NeurologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Wataru Ogawa
- Division of Diabetes and EndocrinologyTokyoJapan
| |
Collapse
|