Endocrine Abstracts

T2DM can occur when our body becomes resistant to insulin. HCV infects hepatocytes and is associated with an increased incidence of T2DM. However, the mechanism by which HCV induces T2DM is poorly understood. Intracellular insulin signalling triggers the activation of the Insulin Receptor Substrate (IRS), leading to glucose transporter-mediated glucose uptake. Insulin signalling is tightly controlled by regulatory proteins called Suppressor Of Cytokine Signalling (SOCS), which bind IRS, thus blocking further signal transduction. We recently discovered the HCV ion channel protein, p 7, independently upregulates SOCS 3. Therefore, this study aimed to determine if HCV-p7 blocks insulin signalling via its upregulation of SOCS 3: a process that may be responsible for the development of T2DM. The Huh 7 hepatocyte cell line was transfected with SOCS 3 or HCV-p7 DNA plasmids, followed by insulin stimulation. Cell lysates were analysed by immunoblotting for pIRS 1, IRS 1, SOCS 3 and Beta-Actin. One-way ANOVA and unpaired t-tests were used to measure statistical differences. We found that both insulin treatment and HCV-p7 expression increased SOCS 3 protein levels, which correlated with reduction in insulin-mediated pIRS 1 (n = 3). Therefore, this study reveals a new mechanism by which HCV-p7 induces insulin resistance in liver hepatocytes and highlights SOCS 3 as a potential therapeutic target to improve insulin sensitivity and cure T2DM.