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BIOLOGICAL ROLES OF NEW TRANSCRIPTION FACTOR FOR GLUCOSE METABOLISM(ChREBP) IN PANCREATIC ISLET CELLS

Research Project

Project/Area Number 15590963
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionKURUME UNIVERSITY SCHOOL OF MEDICINE

Principal Investigator

KAWAGUCHI Takumi  Kurume University School of Medicine, Department of Digestive Disease Information & Research, Assistant, 医学部, 助手 (00320177)

Co-Investigator(Kenkyū-buntansha) HARADA Masaru  Kurume University School of Medicine, Department of Medicine, Assistant Professor, 医学部, 講師 (00241175)
KOGA Hironori  Kurume University School of Medicine, Department of Medicine, Assistant Professor, 医学部, 講師 (90268855)
TANIGUCHI Eitaro  Kurume University School of Medicine, Department of Medicine, Assistant, 医学部, 助手 (50341318)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsChREBP / INS-1 cell / insulin secretion / gene mutation / insulin receptor / diabetes mellitus / HepG2 cell / insulin receptor substrate / リン酸化 / 肝細胞 / insulin receptor substrate 1 / 2 / 2型糖尿病 / INS-1細胞 / Nuclear localization signal / 細胞内局在変化 / siRNA / インスリンプロモータ領域 / 遺伝子導入 / InsZ / luciferase reporter assay
Research Abstract

Diabetes mellitus is characterized by the impairment of glucose metabolism, however, the responsible molecules for the development of diabetes mellitus remains unclear. Recently, we have identified and characterize a transcription factor for glucose metabolism, carbohydrate responsive element binding protein(ChREBP). ChREBP activates the transcripton of liver-type pyruvate kinase gene. The aim of this study is to investigate the biological roles of ChREBP in pancreatic beta cell and hepatocytes, target cells of insulin.
The role of ChREBP in insulin secretion was investigated by using INS-1 cells. By transfection of ChREBP gene into INS-1 cell, ChREBP was overexpressed in INS-1 cell and insulin levels in culture media was altered. We also examined the mutation of ChERBP gene in patients with diabetes mellitus. Although regulation sites of ChREBP were investigated, any mutation of gene was not identified. In addition, we investigated the mechanisms for hepatic insulin resistance. Although there was no significant change in insulin receptor, down-regulation of hepatic insulin receptor substrate 1/2, central molecules for intracellular insulin signaling cascade, was seen in HepG2 cells showing increased insulin resistance.
In this study, we demonstrated the biological roles of ChREBP in INS-1 cells and the involvement of hepatocyte, a target cell of insulin, in the development of insulin resistance. Thus, ChREBP and insulin receptor substrate 1/2 may be responsible molecules for the development of diabetes mellitus.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (18 results)

All 2006 2005 2004

All Journal Article (18 results)

  • [Journal Article] Endothelial progenitor cell transplantation improves the survival follo wing liver injury in mice.2006

    • Author(s)
      Taniguchi E
    • Journal Title

      Gastroenterology 130・2

      Pages: 521-31

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Endothelial progenitor cell transplantation improves the survival following liver injury in mice2006

    • Author(s)
      Taniguchi E
    • Journal Title

      Gastroenterology 130-2

      Pages: 521-531

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Endothelial progenitor cell transplantation improves the survival following liver injury in mice.2006

    • Author(s)
      Taniguchi E
    • Journal Title

      Gastroenterology 130・2

      Pages: 521-531

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Extrahepatic manifestations and insulin resistance in an HCV hyperen demic area.2005

    • Author(s)
      Nagao Y
    • Journal Title

      Int J Mol Med 16・2

      Pages: 291-6

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Causal relationship between hepatitis C virus core and the development of type 2 diabetes mellitus in a hepatitis C virus hyperendemic area : a pilot study.2005

    • Author(s)
      Kawaguchi T
    • Journal Title

      Int J Mol Med 16・1

      Pages: 109-14

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Keratin-containing inclusions affect cell morphology and distribution of cytosolic cellular components.2005

    • Author(s)
      Hanada S
    • Journal Title

      Exp Cell Res 304・2

      Pages: 471-82

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cholestasis in a rat model of graft-versus-host disease is accompanied by alteration of the expression and distribution of tight-junction-asso ciated proteins.2005

    • Author(s)
      Sasatomi K
    • Journal Title

      Int J Mol Med 15・3

      Pages: 431-6

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The Wilson disease protein ATP7B resides in the late endosomes with Rab7 and the Niemann-Pick C1 protein.2005

    • Author(s)
      Harada M
    • Journal Title

      Am J Pathol. 166・2

      Pages: 499-510

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Extrahepatic manifestations and insulin resistance in an HCV hyperendemic area2005

    • Author(s)
      Nagao Y
    • Journal Title

      Int J Mol Med 16-2

      Pages: 291-296

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Causal relationship between hepatitis C virus core and the development of type 2 diabetes mellitus in a hepatitis C virus hyperendemic area : a pilot study2005

    • Author(s)
      Kawaguchi T
    • Journal Title

      Int J Mol Med 16-1

      Pages: 109-114

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Keratin-containing inclusions affect cell morphology and distribution of cytosolic cellular components2005

    • Author(s)
      Hanada S
    • Journal Title

      Exp Cell Res 304-2

      Pages: 471-482

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cholestasis in a rat model of graft-versus-host disease is accompanied by alteration of the expression and distribution of tight-junction-associated proteins2005

    • Author(s)
      Sasatomi K
    • Journal Title

      Int J Mol Med 15-3

      Pages: 431-436

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The Wilson disease protein ATP7B resides in the late endosomes with Rab7 and the Niemann-Pick C1 protein2005

    • Author(s)
      Harada M
    • Journal Title

      Am J Pathol 166-2

      Pages: 499-510

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Extrahepatic manifestations and insulin resistance in an HCV hyperendemic area.2005

    • Author(s)
      Nagao Y
    • Journal Title

      Int J Mol Med 16・2

      Pages: 291-296

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Keratin-containing inclusions affect cell morphology and distribution of cytosolic cellular components.2005

    • Author(s)
      Hanada S
    • Journal Title

      Exp Cell Res. 304・2

      Pages: 471-482

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hepatitis C virus down-regulates insulin receptor substrate 1 and 2 through up-regulation of suppressor of cytokine signaling 3.2004

    • Author(s)
      Kawaguchi T
    • Journal Title

      Am J Pathol. 165・5

      Pages: 1499-1508

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 32004

    • Author(s)
      Kawaguchi T
    • Journal Title

      Am J Pathol 165-5

      Pages: 1499-1508

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hepatitis C virus down-regulates insulin receptor substrate 1 and 2 through up-regulation of suppressor of cytokine signaling 3.2004

    • Author(s)
      Kawaguchi T
    • Journal Title

      Am J Pathol 165・5

      Pages: 1499-1508

    • Related Report
      2004 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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