Abstract
Alcohol exposure impairs myocardium insulin sensitivity, which links to heart dysfunction. miR-155 regulates mTOR signaling pathway and is involved in multiple functions. However, the underlying mechanism of miR-155 in ethanol-induced myocardial insulin resistance remains unclear. Here, in this study we aimed to identify the role of miR-155 in myocardial insulin sensitivity and the involvement of mTOR pathway. H9C2 cells were cultured with or without 100 mM ethanol for 24 h. miR-155-5p inhibitor, miR-155-5p mimics or their respective negative control (inhibitor NC and mimic NC) were transfected to regulate miR-155-5p expression. mTOR signaling, including Ras homolog enriched in brain (Rheb), rapamycin insensitive companion of mTOR (Rictor) and ribosomal protein S6 kinase B2 (S6K2), was investigated by western blotting and qPCR, and insulin responsiveness was evaluated by glucose uptake and phosphorylation of insulin receptor substrate-1 (p-IRS1). The miR-155-5p level increased under ethanol exposure, accompanied by a decrease in glucose uptake, an increase in p-IRS1(ser 307) and activation of the mTOR signaling pathway in H9C2 cells. In addition, miR-155-5p downregulation decreased the glucose uptake, increased the p-IRS1(ser 307) level and activated the mTOR signaling pathway. miR-155-5p upregulation increased the glucose uptake, decreased the p-IRS1(ser 307) level and suppressed the mTOR signaling pathway. Collectively, these findings suggest miR-155-5p upregulation ameliorates myocardial insulin resistance via mTOR signaling in vitro, and miR-155-5p downregulation attenuates myocardial insulin resistance, which might become a potential therapeutic target for alcohol-induced cardiomyopathy.