Hepatitis C virus E2 protein involve in insulin resistance through an impairment of Akt/PKB and GSK3[beta] signaling in hepatocytes

Background Hepatitis C virus (HCV) infection may cause liver diseases of various severities ranging from primary acute infection to life-threatening diseases, such as cirrhosis or hepatocellular carcinoma with poor prognosis. According to clinical findings, HCV infection may also lead to some extra-...

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Bibliographic Details
Published inBMC gastroenterology Vol. 12
Main Authors Hsieh, Ming-Ju, Lan, Kuang-Ping, Liu, Hao-Yu, Zhang, Xiao-Zong, Lin, Yaw-Feng, Chen, Tzy-Yen, Chiou, Hui-Ling
Format Journal Article
LanguageEnglish
Published London BioMed Central Ltd 21.06.2012
BioMed Central
Subjects
Analysis
Dextrose
Gastroenterology
Glucose
Glucose metabolism
Glycogen
Health aspects
Hepatitis C virus
Infection
Insulin
Insulin resistance
Kinases
Liver
Liver cirrhosis
Medical research
Medicine, Experimental
Physiological aspects
Prognosis
Proteins
Synthesis
Type 2 diabetes
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Summary:Background Hepatitis C virus (HCV) infection may cause liver diseases of various severities ranging from primary acute infection to life-threatening diseases, such as cirrhosis or hepatocellular carcinoma with poor prognosis. According to clinical findings, HCV infection may also lead to some extra-hepatic symptoms, including type 2 diabetes mellitus (DM). Since insulin resistance is the major etiology for type 2 DM and numerous evidences showed that HCV infection associated with insulin resistance, the involvement of E2 in the pathogenesis of type 2 DM and underlying mechanisms were investigated in this study. Methods Reverse transcription and real-time PCR, Western blot assay, Immunoprecipitation, Glucose uptake assay and analysis of cellular glycogen content. Results Results showed that E2 influenced on protein levels of insulin receptor substrate-1 (IRS-1) and impaired insulin-induced Ser308 phosphorylation of Akt/PKB and Ser9 phosphorylation of GSK3[beta] in Huh7 cells, leading to an inhibition of glucose uptake and glycogen synthesis, respectively, and eventually insulin resistance. Conclusions Therefore, HCV E2 protein indeed involved in the pathogenesis of type 2 DM by inducing insulin resistance. Keywords: Hepatitis C virus, E2 envelope protein, Type 2 diabetes mellitus, Insulin resistance, Insulin receptor substrate-1 (IRS-1), GSK3[beta]
ISSN:1471-230X
1471-230X
DOI:10.1186/1471-230X-12-74