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.

Journal of Hepatology
|March 24, 2009
PubMed
Abstract

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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