Irisin improves insulin resistance by inhibiting autophagy through the PI3K/Akt pathway in H9c2 cells

• Published in: Gene Vol. 769; p. 145209
• Main Authors: Song, Rongjing, Zhao, Xuecheng, Cao, Rong, Liang, Yuerun, Zhang, Da-Qi, Wang, Rong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.02.2021
• Subjects: Animals; Autophagy; Autophagy - drug effects; Cardiomyocyte; Cell Line; Cell Survival; Diabetic cardiomyopathy; Fibronectins - pharmacology; Humans; Insulin Resistance; MAP Kinase Signaling System - drug effects; Myoblasts, Cardiac - drug effects; Myoblasts, Cardiac - metabolism; Myokine; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Rats; Recombinant Fusion Proteins - pharmacology; RAP; T2DM; Ab; SDS; IR; Autophagy; MDC; DCM; mAb; Myokine; PA; DMEM; BSA; Atg; ANOVA; Cardiomyocyte; FBS; Diabetic cardiomyopathy; Insulin resistance; SEM
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2020.145209

•Irisin can improve the IR induced by PA in rat cardiomyocyte H9c2 cells.•Irisin inhibits PA-induced autophagy thereby improving IR.•Irisin improves IR by activating the PI3K/Akt pathway in H9c2 cells. As an important complication of diabetes mellitus, diabetic cardiomyopathy (DCM) is thought to arise as a result of insulin resistance (IR) in cardiomyocytes. Improving IR in cardiomyocytes may therefore be a way to treat DCM. A recently discovered myokine, irisin, has been shown to be significantly associated with increased insulin sensitivity both in clinical and pre-clinical studies of diabetes mellitus. Based on previously research, we hypothesized that irisin may be a potential candidate for increasing the insulin sensitivity of cardiomyocytes. The aim of the present study was to examine the ability of irisin to affect IR induced by treatment of rat cardiomyocyte H9c2 cells with palmitic acid (PA) and to explore its underlying mechanism. Differentiated H9c2 cells were treated with 500 μM PA, 200 ng/mL irisin, and 500 μM PA + 200 ng/mL irisin with or without 100 nM rapamycin (RAP) for 24 h. We found that coincubation with 200 ng/mL irisin for 24 h significantly increased insulin-stimulated glucose consumption compared to the 500 μM PA group alone. Additionally, coincubation with irisin significantly alleviated the degree of autophagy compared to the 500 μM PA group alone as evidenced by monodansylcadaverine (MDC) fluorescence, the LC3II/LC3I protein levels ratio, and the protein levels of Atg5 and Atg7. Coincubation with irisin increased the levels of PI3Kp110α, pAkt and Akt compared to the 500 μM PA group alone. All these effects of irisin were reversed by RAP. Our results indicate that irisin improves IR in H9c2 cells, possibly in part by inhibiting autophagy through activating the PI3K/Akt pathway.