scholarly journals Time-restricted feeding prevents deleterious metabolic effects of circadian disruption through epigenetic control of β cell function

2021 ◽  
Vol 7 (51) ◽  
Author(s):  
Matthew R. Brown ◽  
Satish K. Sen ◽  
Amelia Mazzone ◽  
Tracy K. Her ◽  
Yuning Xiong ◽  
...  
2017 ◽  
Vol 123 ◽  
pp. 24-36 ◽  
Author(s):  
Diana Bernstein ◽  
Maria L. Golson ◽  
Klaus H. Kaestner

2010 ◽  
Vol 162 (4) ◽  
pp. 729-735 ◽  
Author(s):  
Daniël H van Raalte ◽  
Valentina Nofrate ◽  
Mathijs C Bunck ◽  
Thijs van Iersel ◽  
Jeroen Elassaiss Schaap ◽  
...  

ObjectiveGlucocorticoids (GCs), such as prednisolone, are associated with adverse metabolic effects, including glucose intolerance and diabetes. In contrast to the well known GC-induced insulin resistance, the effects of GCs on β-cell function are less well established. We assessed the acute and short-term effects of prednisolone treatment on β-cell function in healthy men.Research design and methodsA randomised, double-blind, placebo-controlled trial consisting of two protocols was conducted. In protocol 1 (n=6), placebo and a single dose of 75 mg of prednisolone were administered. In protocol 2 (n=23), participants received 30 mg of prednisolone daily or placebo for 15 days. Both empirical and model-based parameters of β-cell function were calculated from glucose, insulin and C-peptide concentrations obtained during standardised meal tests before and during prednisolone treatment (protocols 1 and 2), and 1 day after cessation of treatment (protocol 2).ResultsSeventy-five milligrams of prednisolone acutely increased the area under the postprandial glucose curve (AUCgluc;P=0.005), and inhibited several parameters of β-cell function, including AUCc-pep/AUCglucratio (P=0.004), insulinogenic index (P=0.007), glucose sensitivity (P=0.02) and potentiation factor ratio (PFR;P=0.04). A 15-day treatment with prednisolone increased AUCgluc(P<0.001), despite augmented C-peptide secretion (P=0.05). β-cell function parameters were impaired, including the fasting insulin secretory tone (P=0.02) and PFR (P=0.007).ConclusionsAcute and short-term exposure to prednisolone impairs different aspects of β-cell function, which contribute to its diabetogenic effects.


2019 ◽  
Vol 133 (22) ◽  
pp. 2317-2327 ◽  
Author(s):  
Nicolás Gómez-Banoy ◽  
James C. Lo

Abstract The growing prevalence of obesity and its related metabolic diseases, mainly Type 2 diabetes (T2D), has increased the interest in adipose tissue (AT) and its role as a principal metabolic orchestrator. Two decades of research have now shown that ATs act as an endocrine organ, secreting soluble factors termed adipocytokines or adipokines. These adipokines play crucial roles in whole-body metabolism with different mechanisms of action largely dependent on the tissue or cell type they are acting on. The pancreatic β cell, a key regulator of glucose metabolism due to its ability to produce and secrete insulin, has been identified as a target for several adipokines. This review will focus on how adipokines affect pancreatic β cell function and their impact on pancreatic β cell survival in disease contexts such as diabetes. Initially, the “classic” adipokines will be discussed, followed by novel secreted adipocyte-specific factors that show therapeutic promise in regulating the adipose–pancreatic β cell axis.


2004 ◽  
Vol 9 (4) ◽  
pp. 367-373
Author(s):  
Soo-Bong Choi ◽  
Chun-Hee Park ◽  
Dong-Wha Jun ◽  
Jin-Sun Jang ◽  
Sun-Min Park

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lina Sakhneny ◽  
Alona Epshtein ◽  
Limor Landsman

Abstractβ-Cells depend on the islet basement membrane (BM). While some islet BM components are produced by endothelial cells (ECs), the source of others remains unknown. Pancreatic pericytes directly support β-cells through mostly unidentified secreted factors. Thus, we hypothesized that pericytes regulate β-cells through the production of BM components. Here, we show that pericytes produce multiple components of the mouse pancreatic and islet interstitial and BM matrices. Several of the pericyte-produced ECM components were previously implicated in β-cell physiology, including collagen IV, laminins, proteoglycans, fibronectin, nidogen, and hyaluronan. Compared to ECs, pancreatic pericytes produce significantly higher levels of α2 and α4 laminin chains, which constitute the peri-islet and vascular BM. We further found that the pericytic laminin isoforms differentially regulate mouse β-cells. Whereas α2 laminins promoted islet cell clustering, they did not affect gene expression. In contrast, culturing on Laminin-421 induced the expression of β-cell genes, including Ins1, MafA, and Glut2, and significantly improved glucose-stimulated insulin secretion. Thus, alongside ECs, pericytes are a significant source of the islet BM, which is essential for proper β-cell function.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 752.2-753
Author(s):  
J. C. Quevedo-Abeledo ◽  
F. Genre ◽  
J. Rueda-Gotor ◽  
A. Corrales ◽  
V. Hernández-Hernández ◽  
...  

Background:Insulin resistance (IR) is a state in which a given concentration of insulin is associated with a subnormal glucose response. IR constitutes a major underlying abnormality driving cardiovascular disease in the general population and has been linked to inflammatory diseases. In this sense, several reports have confirmed that inflammation worsens IR and impairs pancreatic β-cell function in inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus.Objectives:In this study we aimed to determine the prevalence of IR in patients with spondyloarthritis (SpA) compared to controls, and whether IR can be explained by disease-related features in SpA patients.Methods:Study of 577 subjects, 306 patients diagnosed with SpA according to ASAS criteria and 271 controls. Insulin and C-peptide serum levels, IR and β-cell function (%B) indexes by homeostatic model assessment (HOMA2), and lipid profiles were assessed in patients and controls. A multivariate regression analysis was performed to evaluate the differences in IR indexes between patients and controls and to determine how IR is associated with disease-related characteristics.Results:SpA patients showed higher serum levels of insulin (8.7 [4.8-15.9] vs. 8.0 [5.7-11.2] uU/ml, p=0.001) and C peptide (1.4 [0.7-2.5] vs. 1.2 [0.7-1.7] ng/ml, p=0.000) than controls in the univariate analysis. Similarly, HOMA2-B% and IR were all significantly higher in SpA patients. These differences were still evident when the comparisons were made after the multivariate analysis had been adjusted for traditional IR-related factors (sex, age, BMI, hypertension, dyslipidemia, smoking and, cholesterol), glucocorticoids intake, insulin and C-peptide. Moreover, HOMA2-B% and HOMA2-IR scores, both calculated with insulin or C-peptide, yielded statistically higher significant values in SpA patients than controls.Classic IR-related factors (age, BMI, waist circumference, hypertension, obesity, dyslipidemia, atherogenic index, and triglycerides), as well as CRP serum levels, were all related, to a greater or lesser degree, with IR and β-cell function. Regarding disease-related data, ASDAS-CRP, BASFI and BASMI scores were positively associated with IR; and BASMI and BASDAI scores were positively related to HOMA2-%B-C peptide. Moreover, the use of NSAID and prednisone were, respectively, positive and negatively related to β-cell function. However, only some of the associations of the univariate analysis were maintained after adjusting for confounders. In this sense, disease duration (beta coefficient 2 [95% CI 1-3], p=0.001) and positivity for HLA-B27 (beta coefficient 30 [95% CI 12-49], p=0.002) were associated with higher β-cell functionality after the multivariate analysis.Conclusion:Patients with SpA have an increased IR compared to controls. SpA disease-related data like disease duration and HLA-B27 are independently associated with β-cell dysfunction.Disclosure of Interests:Juan Carlos Quevedo-Abeledo Speakers bureau: Abbvie, Fernanda Genre: None declared, Javier Rueda-Gotor: None declared, Alfonso Corrales Speakers bureau: Abbvie, Vanessa Hernández-Hernández Speakers bureau: Pfizer, Abbvie, MSD, Natalia Fañanas-Rodríguez: None declared, Bernardo Lavín-Gómez: None declared, delgado frias esmeralda Speakers bureau: Pfizer, Abbvie, MSD, Antonia de Vera-González: None declared, Alejandra Delgado-González: None declared, Laura de Armas-Rillo: None declared, Maria Teresa García-Unzueta: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Iván Ferraz-Amaro Grant/research support from: Pfizer, Abbvie, Speakers bureau: Pfizer, Abbvie, MSD.


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