Hepatitis C virus infection and insulin resistance

Figure 1 Schematic showing the interference of Hepatitis C virus in the insulin signaling pathway. Hepatitis C virus (HCV) core protein is known to up regulate Ser³¹² phosphorylation of insulin receptor substrate (IRS)-1 leading to degradation of IRS-1, the key molecule involved in propagation of insulin signal downstream from the insulin receptor (IR). HCV infection is also known to down regulate TSC1/TSC2 complex, resulting in subsequent upregulation of mTOR/S6K1 which leads to Ser¹¹⁰¹ phosphorylation of IRS-1 and its subsequent degradation. A role of HCV mediated upregulation of SOCS3 and tumor necrosis factor-α (TNF-α) has also been proposed which leads to degradation and blocking of IRS-1 function. HCV also upregulates glucose 6 phosphatase (G6P), phosphoenolpyruvate carboxykinase 2 (PCK2) leading to increased glucose production, and down regulates glucose transporter (GLUT)-4, GLUT-2, leading to decreased glucose uptake by hepatocytes. Overall, these alterations lead to insulin resistance. mTOR: Mammalian target of rapamycin.