School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
BMC Gastroenterol. 2012 Jun 21;12:74. doi: 10.1186/1471-230X-12-74.
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.
Reverse transcription and real-time PCR, Western blot assay, Immunoprecipitation, Glucose uptake assay and analysis of cellular glycogen content.
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.
Therefore, HCV E2 protein indeed involved in the pathogenesis of type 2 DM by inducing insulin resistance.
丙型肝炎病毒（HCV）感染可导致从急性原发性感染到危及生命的疾病等各种严重程度的肝脏疾病，如肝硬化或肝细胞癌，预后不良。根据临床发现，HCV 感染也可能导致一些肝外症状，包括 2 型糖尿病（DM）。由于胰岛素抵抗是 2 型 DM 的主要病因，并且有大量证据表明 HCV 感染与胰岛素抵抗有关，因此本研究探讨了 E2 在 2 型 DM 发病机制中的作用及其潜在机制。
逆转录和实时 PCR、Western blot 分析、免疫沉淀、葡萄糖摄取分析和细胞糖原含量分析。
结果表明，E2 影响 Huh7 细胞中胰岛素受体底物-1（IRS-1）的蛋白水平，并损害胰岛素诱导的 Akt/PKB 的 Ser308 磷酸化和 GSK3β 的 Ser9 磷酸化，分别导致葡萄糖摄取和糖原合成抑制，最终导致胰岛素抵抗。
因此，HCV E2 蛋白通过诱导胰岛素抵抗确实参与了 2 型 DM 的发病机制。
