Glucose-Stimulated Upregulation of GLUT2 Gene Is Mediated by Sterol Response Element–Binding Protein-1c in the Hepatocytes

  1. Seung-Soon Im123,
  2. Seung-Youn Kang13,
  3. So-Youn Kim123,
  4. Ha-il Kim23,
  5. Jae-Woo Kim24,
  6. Kyung-Sup Kim1234 and
  7. Yong-Ho Ahn123
  1. 1Brain Korea 21 Project for Medical Sciences, Yonsei University, Seoul, Korea
  2. 2Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea
  3. 3Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, Seoul, Korea
  4. 4Institute of Genetic Science, Yonsei University College of Medicine, Seoul, Korea
  1. Address correspondence and reprint requests to Yong-Ho Ahn, MD, PhD, Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul 120-752, Korea. E-mail: yha111{at}yumc.yonsei.ac.kr

Abstract

GLUT2 is mainly expressed in the liver, β-cells of the pancreas, and the basolateral membrane of kidney proximal tubules and plays an important role in glucose homeostasis in living organisms. The transcription of the GLUT2 gene is known to be upregulated in the liver during postprandial hyperglycemic states or in type 2 diabetes. However, a molecular mechanism by which glucose activates GLUT2 gene expression is not known. In this study, we report evidence that sterol response element–binding protein (SREBP)-1c plays a key role in glucose-stimulated GLUT2 gene expression. The GLUT2 promoter reporter is activated by SREBP-1c, and the activation is inhibited by a dominant-negative form of SREBP-1c (SREBP-1c DN). Adenoviral expression of SREBP-1c DN suppressed glucose-stimulated GLUT2 mRNA level in primary hepatocytes. An electrophoretic mobility shift assay and mutational analysis of the GLUT2 promoter revealed that SREBP-1c binds to the −84/−76 region of the GLUT2 promoter. Chromatin immunoprecipitation revealed that the binding of SREBP-1c to the −84/−76 region was increased by glucose concentration in a dose-dependent manner. These results indicate that SREBP-1c mediates glucose-stimulated GLUT2 gene expression in hepatocytes.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted March 14, 2005.
    • Received October 21, 2004.
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