Rabbit Anti-Human IRS1 Polyclonal antibody

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.

Despite the consensus that neuro-inflammation and insulin resistance (IR) are two hallmarks of Alzheimer disease (AD), the molecular mechanisms responsible for the development of IR remain uncharacterized. MAPKs are signaling molecules that are implicated in the pathology of AD and have a role in IR development. Given that inflammatory mediators are shown to interfere with insulin signaling pathway in different cell types, the present work aimed to investigate whether neuro-inflammation induced memory loss is associated with hippocampal IR and whether insulin treatment protects against this IR. Subsequently, possible roles of MAPKs in this situation were investigated. Male Wistar rats were cannulated, and LPS (15 mu g, day 0), insulin (3 mU) or saline (vehicle) were administered intra-cerebroventricularly (ICV) (days 1-6). Spatial memory performance was assessed during days 7-10 by Morris Water Maze test. Consequently, analysis of the amount of hippocampal phosphorylated forms of P38, JNK, ERK, IRS1 (ser307) and Akt (ser473) were done by Western blot. The outcomes indicated that while LPS induced memory loss and hippocampal IR (shown by elevated IRS1 and decreased Akt phosphorylation), insulin treatment nullified these effects. Molecular results also showed that LPS mediated IR and memory loss are associated with P38 but not JNK and ERK activation; this P38 activation was reversed by insulin treatment. These observations implied that one of the ways by which neuro-inflammation participates in AD is via induction of IR. It seems that this IR is mainly mediated by P38. Therefore, P38 could be considered as a molecular target for preventing IR development.