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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...

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Autores principales: Hsieh, Ming-Ju, Lan, Kuang-Ping, Liu, Hao-Yu, Zhang, Xiao-Zong, Lin, Yaw-Feng, Chen, Tzy-Yen, Chiou, Hui-Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464126/
https://www.ncbi.nlm.nih.gov/pubmed/22721429
http://dx.doi.org/10.1186/1471-230X-12-74
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author Hsieh, Ming-Ju
Lan, Kuang-Ping
Liu, Hao-Yu
Zhang, Xiao-Zong
Lin, Yaw-Feng
Chen, Tzy-Yen
Chiou, Hui-Ling
author_facet Hsieh, Ming-Ju
Lan, Kuang-Ping
Liu, Hao-Yu
Zhang, Xiao-Zong
Lin, Yaw-Feng
Chen, Tzy-Yen
Chiou, Hui-Ling
author_sort Hsieh, Ming-Ju
collection PubMed
description 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.
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spelling pubmed-34641262012-10-05 Hepatitis C virus E2 protein involve in insulin resistance through an impairment of Akt/PKB and GSK3β signaling in hepatocytes Hsieh, Ming-Ju Lan, Kuang-Ping Liu, Hao-Yu Zhang, Xiao-Zong Lin, Yaw-Feng Chen, Tzy-Yen Chiou, Hui-Ling BMC Gastroenterol Research Article 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. BioMed Central 2012-06-21 /pmc/articles/PMC3464126/ /pubmed/22721429 http://dx.doi.org/10.1186/1471-230X-12-74 Text en Copyright ©2012 Hsieh et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hsieh, Ming-Ju
Lan, Kuang-Ping
Liu, Hao-Yu
Zhang, Xiao-Zong
Lin, Yaw-Feng
Chen, Tzy-Yen
Chiou, Hui-Ling
Hepatitis C virus E2 protein involve in insulin resistance through an impairment of Akt/PKB and GSK3β signaling in hepatocytes
title Hepatitis C virus E2 protein involve in insulin resistance through an impairment of Akt/PKB and GSK3β signaling in hepatocytes
title_full Hepatitis C virus E2 protein involve in insulin resistance through an impairment of Akt/PKB and GSK3β signaling in hepatocytes
title_fullStr Hepatitis C virus E2 protein involve in insulin resistance through an impairment of Akt/PKB and GSK3β signaling in hepatocytes
title_full_unstemmed Hepatitis C virus E2 protein involve in insulin resistance through an impairment of Akt/PKB and GSK3β signaling in hepatocytes
title_short Hepatitis C virus E2 protein involve in insulin resistance through an impairment of Akt/PKB and GSK3β signaling in hepatocytes
title_sort hepatitis c virus e2 protein involve in insulin resistance through an impairment of akt/pkb and gsk3β signaling in hepatocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464126/
https://www.ncbi.nlm.nih.gov/pubmed/22721429
http://dx.doi.org/10.1186/1471-230X-12-74
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