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Updated: Jun 24, 2026

A Protocol for Analyzing Hepatitis C Virus Replication
Published on: June 26, 2014
HCV replication suppresses cellular glucose uptake through down-regulation of cell surface expression of glucose
Daisuke Kasai1, Tetsuya Adachi, Lin Deng
1Division of Microbiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
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 (IFN). 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.
Insights
Hepatitis C virus (HCV) replication lowers glucose uptake in liver cells by reducing glucose transporter 2 (GLUT2) expression. Interferon treatment reversed these effects, suggesting a potential therapeutic target for HCV-related diabetes.
Area of Science:
- Hepatology
- Virology
- Metabolic Diseases
Background:
- Persistent hepatitis C virus (HCV) infection is linked to extrahepatic diseases like diabetes.
- Understanding the mechanisms connecting HCV and glucose metabolism is crucial.
Purpose of the Study:
- To investigate the impact of HCV replication on hepatocyte glucose uptake.
- To examine the effect of HCV on the expression of glucose transporters GLUT2 and GLUT1.
Main Methods:
- Utilized cell culture models with HCV replicons (SGR, FGR) and HCV-infected cells.
- Assessed glucose uptake, GLUT2/GLUT1 surface expression, mRNA levels, and promoter activity.
- Analyzed liver tissue samples from HCV-infected and non-infected patients.
- Evaluated the effect of interferon (IFN) treatment.
Main Results:
- HCV replication suppressed glucose uptake and surface expression of GLUT2 and GLUT1.
- GLUT2 mRNA expression and promoter activity were reduced in HCV-infected cells.
- Interferon treatment normalized glucose uptake and GLUT2 expression.
- Reduced GLUT2 expression was observed in liver tissues from HCV patients.
Conclusions:
- HCV replication down-regulates hepatocyte GLUT2 expression at transcriptional and potentially intracellular trafficking levels.
- This down-regulation contributes to reduced glucose uptake in HCV infection.
- Interferon therapy can restore normal glucose transport mechanisms.
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