Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 883-894 |
| Number of pages | 12 |
| Journal | Journal of Hepatology |
| Volume | 50 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2009 |
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Keywords
- Diabetes mellitus
- Down-regulation
- Glucose uptake
- GLUT1
- GLUT2
- Hepatitis C virus
- Hepatocyte
- Interferon
- Replicon
ASJC Scopus subject areas
- Hepatology
Cite this
HCV replication suppresses cellular glucose uptake through down-regulation of cell surface expression of glucose transporters. / Kasai, Daisuke; Adachi, Tetsuya; Deng, Lin; Nagano-Fujii, Motoko; Sada, Kiyonao; Ikeda, Masanori; Kato, Nobuyuki; Ide, Yoshi Hiro; Shoji, Ikuo; Hotta, Hak.
In: Journal of Hepatology, Vol. 50, No. 5, 05.2009, p. 883-894.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - HCV replication suppresses cellular glucose uptake through down-regulation of cell surface expression of glucose transporters
AU - Kasai, Daisuke
AU - Adachi, Tetsuya
AU - Deng, Lin
AU - Nagano-Fujii, Motoko
AU - Sada, Kiyonao
AU - Ikeda, Masanori
AU - Kato, Nobuyuki
AU - Ide, Yoshi Hiro
AU - Shoji, Ikuo
AU - Hotta, Hak
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
KW - Diabetes mellitus
KW - Down-regulation
KW - Glucose uptake
KW - GLUT1
KW - GLUT2
KW - Hepatitis C virus
KW - Hepatocyte
KW - Interferon
KW - Replicon
UR - http://www.scopus.com/inward/record.url?scp=64549151555&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=64549151555&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2008.12.029
DO - 10.1016/j.jhep.2008.12.029
M3 - Article
VL - 50
SP - 883
EP - 894
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 5
ER -