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.

Metformin‐induced autophagy and irisin improves INS‐1 cell function and survival in high‐glucose environment via AMPK/SIRT1/PGC‐1α signal pathway

“…In previous studies, appropriate increase in circulating irisin can rescue insulin sensitivity of C57BL/6 mice with diet‐induced insulin resistance (Lopez‐Legarrea et al, ). Similarly, irisin can cause the reduced apoptosis of INS‐1 cells induced by high glucose and the increased secretion of insulin (Liu et al, ). In the present study, the significantly decreased irisin was also detected during the exposure to high‐glucose environment, while restored by metformin.…”

Irisin increases the expression of anorexigenic and neurotrophic genes in mouse brain

“…It should be noted that, as of today, there is no evidence that circulating irisin may affect body weight in nondiabetic mice. Moreover, the results on the ability of irisin to reduce body weight and food intake in diabetic mice or rats have been conflicting . Indeed, it is possible that the effects of irisin administration on food intake may be dependent upon the timing and/or route of administration.…”

“…Moreover, the results on the ability of irisin to reduce body weight and food intake in diabetic mice or rats have been conflicting. [17][18][19][20][21][22][23][24][25]31 Indeed, it is possible that the effects of irisin administration on food intake may be dependent upon the timing and/or route of administration. The reported irisin-induced increase in food intake (but not in body weight) in nonobese, nondiabetic rats occurred following intracerebroventricular infusion of the hormone for 7 days and was associated with increased circulating ghrelin and decreased serum leptin and POMC mRNA levels in the hypothalamus.…”

“…[13][14][15] Although it was demonstrated that irisin expression is detectable around the paraventricular nucleus region in human hypothalamic sections where it colocalizes with NPY, 16 the potential role of irisin in the regulation of body weight and food intake is still unclear. Indeed, irisin administration has been shown to promote weight loss in diabetic mice or rats, [17][18][19][20][21][22] but other studies showed no differences in body weight between diabetic mice receiving irisin or not. [23][24][25] As of today, no studies have examined the potential effects of irisin treatment on body weight changes in nondiabetic control mice.…”

Irisin Ameliorates Glucolipotoxicity-Associated β-Cell Dysfunction and Apoptosis via AMPK Signaling and Anti-Inflammatory Actions

“…Regarding the regulatory actions on β cells, it has been reported that irisin administration attenuates β-cell apoptosis and restores β-cell function under glucotoxic condition [22]. In addition, a recent study has shown that irisin suppresses apoptosis in β cells and islets under lipotoxic condition via modulation of protein kinase B/B-cell lymphoma 2 (BCL2) signaling pathway [23].…”