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Logo of bmcgastBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Gastroenterology
 
BMC Gastroenterol. 2012; 12: 74.
Published online Jun 21, 2012. doi:  10.1186/1471-230X-12-74
PMCID: PMC3464126
Hepatitis C virus E2 protein involve in insulin resistance through an impairment of Akt/PKB and GSK3β signaling in hepatocytes
Ming-Ju Hsieh,1 Kuang-Ping Lan,2 Hao-Yu Liu,1 Xiao-Zong Zhang,3 Yaw-Feng Lin,4 Tzy-Yen Chen,corresponding author5,6 and Hui-Ling Chioucorresponding author1,7
1School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
2Department of Nursing, Kaomei College of Health Care & Management, Kaohsiung, Taiwan
3Department of Laboratory, CiShan Hospital, Department of Health, Kaohsiung, Taiwan
4Department of Physical Education, National Pingtung University of Education, Pingtung, Taiwan
5Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
6Department of Internal Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
7Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan
corresponding authorCorresponding author.
Ming-Ju Hsieh: kaross1006/at/hotmail.com; Kuang-Ping Lan: lankping/at/gmail.com; Hao-Yu Liu: a_how1218/at/yahoo.com.tw; Xiao-Zong Zhang: barkley34/at/mail.chis.doh.gov.tw; Yaw-Feng Lin: lyf/at/mail.npue.edu.tw; Tzy-Yen Chen: cshy042/at/csh.org.tw; Hui-Ling Chiou: hlchiou/at/csmu.edu.tw
Received March 1, 2012; Accepted June 21, 2012.
Abstract
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.
Keywords: Hepatitis C virus, E2 envelope protein, Type 2 diabetes mellitus, Insulin resistance, Insulin receptor substrate-1 (IRS-1), GSK3β
Articles from BMC Gastroenterology are provided here courtesy of
BioMed Central