Hepatitis C virus E2 protein involve in insulin resistance through an impairment of Akt/PKB and GSK3β 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-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 GSK3β 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.
School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
Ming-Ju
MJ
Hsieh
Kuang-Ping
KP
Lan
Hao-Yu
HY
Liu
Xiao-Zong
XZ
Zhang
Yaw-Feng
YF
Lin
Tzy-Yen
TY
Chen
Hui-Ling
HL
Chiou
D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000821:virology*; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D016174:Hepacivirus / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; D012694:Serine; D006003:Glycogen; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D005947:Glucose