title: Effects and underlying mechanisms of irisin on the proliferation and apoptosis of pancreatic β cells.
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.
authors.affiliation: Department of Endocrinology, Shanxi DAYI Hospital, Shanxi Medical University, Taiyuan, China.
authors.forename: Shiwei
authors.identifier: http://orcid.org/0000-0002-7816-3091
authors.initials: S
authors.lastname: Liu
authors.affiliation: Graduate School of Shanxi Medical University, Taiyuan, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Du
authors.affiliation: Graduate School of Shanxi Medical University, Taiyuan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Graduate School of Shanxi Medical University, Taiyuan, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Wang
authors.affiliation: Graduate School of Shanxi Medical University, Taiyuan, China.
authors.forename: Ruixue
authors.initials: R
authors.lastname: Duan
authors.affiliation: Graduate School of Shanxi Medical University, Taiyuan, China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Graduate School of Shanxi Medical University, Taiyuan, China.
authors.forename: Yaru
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Graduate School of Shanxi Medical University, Taiyuan, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D005353:Fibronectins / Q000008:administration & dosage / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; C583676:FNDC5 protein, rat; D005353:Fibronectins; D007004:Hypoglycemic Agents