title: Hepatitis C virus infection and insulin resistance.
abstract: Approximately 170 million people worldwide are chronically infected with hepatitis C virus (HCV). Chronic HCV infection is the leading cause for the development of liver fibrosis, cirrhosis, hepatocellular carcinoma (HCC) and is the primary cause for liver transplantation in the western world. Insulin resistance is one of the pathological features in patients with HCV infection and often leads to development of type II diabetes. Insulin resistance plays an important role in the development of various complications associated with HCV infection. Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis, steatosis, HCC and resistance to anti-viral treatment. Thus, HCV associated insulin resistance is a therapeutic target at any stage of HCV infection. HCV modulates normal cellular gene expression and interferes with the insulin signaling pathway. Various mechanisms have been proposed in regard to HCV mediated insulin resistance, involving up regulation of inflammatory cytokines, like tumor necrosis factor-α, phosphorylation of insulin-receptor substrate-1, Akt, up-regulation of gluconeogenic genes like glucose 6 phosphatase, phosphoenolpyruvate carboxykinase 2, and accumulation of lipid droplets. In this review, we summarize the available information on how HCV infection interferes with insulin signaling pathways resulting in insulin resistance.
authors.affiliation: Sandip K Bose, Ranjit Ray, Department of Molecular Microbiology and Immunology, Saint Louis University, St. Louis, MO 63104, United States.
authors.forename: Sandip K
authors.initials: SK
authors.lastname: Bose
authors.affiliation: Sandip K Bose, Ranjit Ray, Department of Molecular Microbiology and Immunology, Saint Louis University, St. Louis, MO 63104, United States.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Ray
keywords: Anti-viral therapy; Glucose transporter-4; Hepatitis C virus; Insulin receptor substrate 1; Insulin resistance; Lipid metabolism; Protein kinase B; Suppressor of cytokine signaling 3; mammalian target of rapamycin/S6K1