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Effects and underlying mechanisms of irisin on the proliferation and apoptosis of pancreatic β cells

Pancreatic β cell dysfunction and reduction due to glucose toxicity play a crucial role in the development of type 2 diabetes mellitus (T2DM). Irisin, a novel exercise-induced myokine, reduces obesity, improves insulin resistance and lowers blood glucose by promoting the browning of white adipose ti...

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Published in:PloS one 2017-04, Vol.12 (4), p.e0175498
Main Authors: Liu, Shiwei, Du, Fang, Li, Xin, Wang, Mingming, Duan, Ruixue, Zhang, Jiaxin, Wu, Yaru, Zhang, Qi
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Li, Xin
Wang, Mingming
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Zhang, Qi
description Pancreatic β cell dysfunction and reduction due to glucose toxicity play a crucial role in the development of type 2 diabetes mellitus (T2DM). Irisin, a novel exercise-induced myokine, reduces obesity, improves insulin resistance and lowers blood glucose by promoting the browning of white adipose tissue, thereby enhancing thermogenesis and increasing energy expenditure. Recent studies have reported that irisin promotes cell proliferation and protects cells from apoptosis. However, the effects of irisin on pancreatic β cells are unknown. Thus, the aim of this study was to investigate the effects and the potential underlying mechanisms of irisin on pancreatic β cell proliferation and apoptosis induced by high glucose. Both in vitro (INS-1 cells) and in vivo (a T2DM rat model) experiments were conducted. Irisin significantly increased the proliferation of INS-1 cells, with the most significant effect observed at 24 h with 100 ng/ml irisin. Irisin also promoted INS-1 cell proliferation via the ERK and p38 MAPK signaling pathways, protected the cells from high-glucose-induced apoptosis by regulating the expression of caspases, Bad, Bax, Bcl-2 and Bcl-xl, and improved pancreatic β cell function. Irisin significantly reduced the body weight and blood glucose values and increased the serum insulin levels of the diabetic rats. An oral glucose tolerance test (OGTT) indicated that irisin also improved the glucose tolerance of T2DM rats. Together, these findings suggest that irisin may have applications in the prevention and treatment of T2DM because of its protective effect on the secretion of pancreatic β cells.
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Irisin, a novel exercise-induced myokine, reduces obesity, improves insulin resistance and lowers blood glucose by promoting the browning of white adipose tissue, thereby enhancing thermogenesis and increasing energy expenditure. Recent studies have reported that irisin promotes cell proliferation and protects cells from apoptosis. However, the effects of irisin on pancreatic β cells are unknown. Thus, the aim of this study was to investigate the effects and the potential underlying mechanisms of irisin on pancreatic β cell proliferation and apoptosis induced by high glucose. Both in vitro (INS-1 cells) and in vivo (a T2DM rat model) experiments were conducted. Irisin significantly increased the proliferation of INS-1 cells, with the most significant effect observed at 24 h with 100 ng/ml irisin. Irisin also promoted INS-1 cell proliferation via the ERK and p38 MAPK signaling pathways, protected the cells from high-glucose-induced apoptosis by regulating the expression of caspases, Bad, Bax, Bcl-2 and Bcl-xl, and improved pancreatic β cell function. Irisin significantly reduced the body weight and blood glucose values and increased the serum insulin levels of the diabetic rats. An oral glucose tolerance test (OGTT) indicated that irisin also improved the glucose tolerance of T2DM rats. Together, these findings suggest that irisin may have applications in the prevention and treatment of T2DM because of its protective effect on the secretion of pancreatic β cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28394923</pmid><doi>10.1371/journal.pone.0175498</doi><orcidid>https://orcid.org/0000-0002-7816-3091</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adipose tissue
Animals
Apoptosis
Apoptosis - drug effects
Apoptosis - physiology
Bcl protein
Bcl-2 protein
Bcl-x protein
Biology and Life Sciences
Blood
Blood glucose
Blood Glucose - drug effects
Blood Glucose - metabolism
Body weight
Body Weight - drug effects
Body Weight - physiology
Cell growth
Cell proliferation
Cell Proliferation - drug effects
Cell Proliferation - physiology
Cells, Cultured
Cytokines
Diabetes
Diabetes mellitus
Diabetes Mellitus, Experimental - drug therapy
Diabetes Mellitus, Experimental - metabolism
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - metabolism
Energy expenditure
Fibronectins - administration & dosage
Fibronectins - metabolism
Glucose
Glucose tolerance
Glucose Tolerance Test
Hypoglycemic Agents - administration & dosage
Insulin
Insulin resistance
Insulin-Secreting Cells - drug effects
Insulin-Secreting Cells - metabolism
Male
MAP kinase
MAP Kinase Signaling System - drug effects
MAP Kinase Signaling System - physiology
Medicine and Health Sciences
Pancreas
Physical Sciences
Random Allocation
Rats
Rats, Sprague-Dawley
Secretion
Studies
Thermogenesis
Toxicity
title Effects and underlying mechanisms of irisin on the proliferation and apoptosis of pancreatic β cells
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