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

PLoS One. 2017 Apr 10;12(4):e0175498. doi: 10.1371/journal.pone.0175498. eCollection 2017.

Abstract

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.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Body Weight / physiology
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology*
  • Cells, Cultured
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism*
  • Fibronectins / administration & dosage
  • Fibronectins / metabolism*
  • Glucose Tolerance Test
  • Hypoglycemic Agents / administration & dosage
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Male
  • Random Allocation
  • Rats, Sprague-Dawley

Substances

  • Blood Glucose
  • FNDC5 protein, rat
  • Fibronectins
  • Hypoglycemic Agents

Grant support

This research was supported by the National Natural Science Foundation of China (#81200591&81471025), Fund Program for the Scientific Activities of Selected Return Overseas Professionals in Shanxi Province (#2013-251), International Science and Technology Cooperation Project in Shanxi Province (#2015081029), Research Project Supported Shanxi Scholarship Council of China(#2015-109), Transformation of Scientific and Technological Achievements in Shanxi Province(#201604D131003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.