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World J Diabetes. Feb 15, 2014; 5(1): 52-58
Published online Feb 15, 2014. doi: 10.4239/wjd.v5.i1.52
Hepatitis C virus infection and insulin resistance
Sandip K Bose, Ranjit Ray
Sandip K Bose, Ranjit Ray, Department of Molecular Microbiology and Immunology, Saint Louis University, St. Louis, MO 63104, United States
Ranjit Ray, Division of Infectious Diseases, Allergy and Immunology, Edward A Doisy Research Center, St. Louis, MO 63104, United States
Ranjit Ray, Department of Internal Medicine, Saint Louis University, St. Louis, MO 63104, United States
Author contributions: Bose SK performed literature search and wrote the initial draft of the paper; Ray R edited the paper and made additional changes as needed.
Supported by The National Institutes of Health, NO. DK080812
Correspondence to: Ranjit Ray, PhD, Division of Infectious Diseases, Allergy and Immunology, Edward A Doisy Research Center, 1100 S. Grand Blvd., 8th Floor, St. Louis, MO 63104, United States. rayr@slu.edu
Telephone: +1-314- 9779034 Fax: +1-314-7713816
Received: November 9, 2013
Revised: December 20, 2013
Accepted: January 13, 2014
Published online: February 15, 2014
Processing time: 102 Days and 10.3 Hours
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.

Keywords: Hepatitis C virus; Insulin resistance; Insulin receptor substrate 1; Protein kinase B; mammalian target of rapamycin/S6K1; Suppressor of cytokine signaling 3; Glucose transporter-4; Lipid metabolism; Anti-viral therapy

Core tip: Insulin resistance is one of the pathological features in patients with hepatitis C virus (HCV) infection and often leads to development of type II diabetes. Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis, steatosis, hepatocellular carcinoma and resistance to anti-viral treatment. In this review, we summarize the available information on how HCV infection interferes with insulin signaling pathways.