Irisin improves insulin resistance by inhibiting autophagy through the PI3K/Akt pathway in H9c2 cells
Irisin improves insulin resistance by inhibiting autophagy through the PI3K/Akt pathway in H9c2 cells
复制标题
Irisin 通过抑制 H9c2 细胞中 PI3K/Akt 途径的自噬来改善胰岛素抵抗。
DOI：
10.1016/j.gene.2020.145209
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发表时间：
2021-01-06
期刊：
影响因子：
3.5
通讯作者：
Wang, Rong
中科院分区：
文献类型：
--
作者：
Song, Rongjing;Zhao, Xuecheng;Wang, Rong
作为糖尿病的一个重要并发症，糖尿病心肌病（DCM）被认为是由于心肌细胞中的胰岛素抵抗（IR）而引起的。因此，改善心肌细胞的 IR 可能是治疗 DCM 的一种方法。最近发现的肌因子鸢尾素在糖尿病的临床和临床前研究中已被证明与胰岛素敏感性增加显着相关。根据之前的研究，我们假设鸢尾素可能是提高心肌细胞胰岛素敏感性的潜在候选者。本研究的目的是检测鸢尾素对棕榈酸（PA）处理大鼠心肌细胞 H9c2 细胞诱导的 IR 的影响，并探讨其潜在机制。将分化的 H9c2 细胞用 500 mu M PA、200 ng/mL 鸢尾素和 500 mu M PA + 200 ng/mL 鸢尾素（含或不含 100 nM 雷帕霉素 (RAP)）处理 24 小时。我们发现，与单独使用 500 μM PA 组相比，与 200 ng/mL 鸢尾素共孵育 24 小时显着增加了胰岛素刺激的葡萄糖消耗。此外，单丹磺酰尸胺 (MDC) 荧光、LC3II/LC3I 蛋白水平比率以及 Atg5 和 Atg7 的蛋白水平证明，与单独使用 500 mu M PA 组相比，与鸢尾素共孵育显着减轻了自噬程度。与单独使用 500 mu M PA 组相比，与鸢尾素共孵育增加了 PI3Kp110a、pAkt 和 Akt 的水平。 RAP 逆转了鸢尾素的所有这些作用。我们的结果表明，鸢尾素可改善 H9c2 细胞的 IR，部分原因可能是通过激活 PI3K/Akt 途径抑制自噬。
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 mu M PA, 200 ng/mL irisin, and 500 mu M 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 mu M PA group alone. Additionally, coincubation with irisin significantly alleviated the degree of autophagy compared to the 500 mu M 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 PI3Kp110a, pAkt and Akt compared to the 500 mu M 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.