HCV replication suppresses cellular glucose uptake through down-regulation of cell surface expression of glucose transporters
HCV replication suppresses cellular glucose uptake through down-regulation of cell surface expression of glucose transporters
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DOI：
10.1016/j.jhep.2008.12.029
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发表时间：
2009-05-01
影响因子：
25.7
通讯作者：
Hotta, Hak
中科院分区：
文献类型：
--
作者：
Kasai, Daisuke;Adachi, Tetsuya;Hotta, Hak
背景/目的：丙型肝炎病毒（HCV）持续感染可引起肝外疾病，包括糖尿病。本研究探讨了HCV复制对细胞葡萄糖摄取和葡萄糖易化转运蛋白（GLUT）2和1表达的可能影响。方法：采用携带HCV亚基因组RNA复制子（SGR）或HCV全基因组RNA复制子（FGR）的Huh-7.5细胞、HCV感染细胞以及干扰素（IFN）处理的相应细胞。我们还使用了从患者或没有HCV infection.Results：葡萄糖摄取和表面表达GLUT 2和GLUT 1的患者的肝组织样本中抑制SGR，FGR和HCV感染的细胞相比，对照细胞。SGR、FGR和HCV感染的细胞中GLUT 2 mRNA的表达水平低于对照组，但GLUT 1 mRNA的表达水平不低于对照组。荧光素酶报告基因检测显示，SGR、FGR和HCV感染的细胞中GLUT 2启动子活性降低。IFN处理恢复葡萄糖摄取、GLUT 2表面表达、GLUT 2 mRNA表达和GLUT 2启动子活性。此外，GLUT 2的表达减少，从HCV感染patients.Conclusions：HCV复制下调细胞表面表达的GLUT 2部分在转录水平，并可能在细胞内运输水平的建议为GLUT 1，从而降低肝细胞的葡萄糖摄取。(c)2009年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Persistent infection with hepatitis C virus (HCV) causes extrahepatic diseases, including diabetes. We investigated the possible effect(s) of HCV replication on cellular glucose uptake and expression of the facilitative glucose transporter (GLUT) 2 and 1.Methods: We used Huh-7.5 cells harboring either an HCV subgenomic RNA replicon (SGR) or an HCV full-genomic RNA replicon (FGR), HCV-infected cells, and the respective cells treated with interferon (1FN). We also used liver tissue samples obtained from patients with or without HCV infection.Results:Glucose uptake and surface expression of GLUT2 and GLUT1 were suppressed in SGR, FGR and HCV-infected cells compared to the control cells. Expression levels of GLUT2 mRNA, but not GLUT1 mRNA, were lower in SGR, FGR and HCV-infected cells than in the control. Luciferase reporter assay demonstrated decreased GLUT2 promoter activities in SGR, FGR and HCV-infected cells. IFN treatment restored glucose uptake, GLUT2 surface expression, GLUT2 mRNA expression and GLUT2 promoter activities. Also, GLUT2 expression was reduced in hepatocytes of liver tissues obtained from HCV-infected patients.Conclusions: HCV replication down-regulates cell surface expression of GLUT2 partly at the transcriptional level, and possibly at the intracellular trafficking level as suggested for GLUT1, thereby lowering glucose uptake by hepatocytes. (c) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.