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Figure 1. Molecular effects of SOF on impaired insulin response induced by HCV infection. Schematic diagram showing how SOF improves HCV-induced insulin resistance in infected hepatocytes. (A) Critical nodes of insulin signaling implicated in insulin metabolic actions in healthy hepatocytes. (B) HCV induces serine phosphorylation of IRS1, blocking its tyrosine phosphorylation and targets IRS1 for proteosomal degradation. As IRS1 is a critical molecule involved in the transduction of insulin signal from the insulin receptor (IR), its degradation impairs the downstream AKT signalling pathway leading to insulin resistance. (C) SOF reduces IRS1 serine phosphorylation, avoiding its degradation, and further increases its protein content IRS1 in HCV-hepatocytes, recovering insulin signaling through IR/IRS1/PI3K/AKT. SOF: Sofosbuvir; HCV: hepatitis C virus; IRS: insulin receptor substrate.