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.

作为糖尿病的重要并发症，糖尿病性心肌病（DCM）被认为是心肌细胞中胰岛素抵抗（IR）的结果。因此，改善心肌细胞的IR可能是治疗DCM的一种方法。在糖尿病的临床和临床前研究中，最近发现的肌动蛋白虹膜素与胰岛素敏感性的增加显着相关。基于先前的研究，我们假设虹膜素可能是增加心肌细胞胰岛素敏感性的潜在候选药物。本研究的目的是研究虹膜素对棕榈酸（PA）处理大鼠心肌细胞H9c2细胞诱导的IR的能力，并探讨其潜在机制。分化的H9c2细胞用500μMPA，200 ng / mL虹膜素，和500μMPA + 200 ng / mL虹膜素（有或没有100 nM雷帕霉素（RAP））持续24小时。我们发现，与单独的500μMPA组相比，与200 ng / mL虹膜素共孵育24 h显着增加了胰岛素刺激的葡萄糖消耗。此外，与单500丹那莫尸胺（MDC）荧光，LC3II / LC3I蛋白质水平比以及Atg5和Atg7蛋白质水平相比，与单独的500μMPA组相比，与鸢尾素的共孵育显着减轻了自噬的程度。与单独的500μMPA组相比，与虹膜素共孵育可提高PI3Kp110α，pAkt和Akt的水平。RAP可逆转虹膜素的所有这些作用。我们的结果表明，虹膜素可通过激活PI3K / Akt途径抑制自噬来改善H9c2细胞的IR。我们发现，与单独的500μMPA组相比，与200 ng / mL虹膜素共孵育24 h显着增加了胰岛素刺激的葡萄糖消耗。此外，与单500丹那莫尸胺（MDC）荧光，LC3II / LC3I蛋白质水平比以及Atg5和Atg7蛋白质水平相比，与单独的500μMPA组相比，与鸢尾素的共孵育显着减轻了自噬的程度。与单独的500μMPA组相比，与虹膜素共孵育可提高PI3Kp110α，pAkt和Akt的水平。RAP可逆转虹膜素的所有这些作用。我们的结果表明，虹膜素可通过激活PI3K / Akt途径抑制自噬来改善H9c2细胞的IR。我们发现，与单独的500μMPA组相比，与200 ng / mL虹膜素共孵育24 h显着增加了胰岛素刺激的葡萄糖消耗。此外，与单500丹那莫尸胺（MDC）荧光，LC3II / LC3I蛋白质水平比以及Atg5和Atg7蛋白质水平相比，与单独的500μMPA组相比，与鸢尾素的共孵育显着减轻了自噬的程度。与单独的500μMPA组相比，与虹膜素共孵育可提高PI3Kp110α，pAkt和Akt的水平。RAP可逆转虹膜素的所有这些作用。我们的结果表明，虹膜素可通过激活PI3K / Akt途径抑制自噬来改善H9c2细胞的IR。