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Development of a simple screening system for the discovery of a new drug for diabetes

Research Project

Project/Area Number 08558074
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Functional biochemistry
Research InstitutionThe University of Tokushima

Principal Investigator

EBINA Yousuke  The University of Tokushima, Institute for Enzyme Research, Professor, 分子酵素学研究センター, 教授 (00112227)

Co-Investigator(Kenkyū-buntansha) ASAHI Yoshihiko  Otsuka Pharmaceutical Co., Ltd.Tokushima Institute, 徳島研究所, 研究員
KISHI Kazuhiro  The University of Tokushima, Institute for Enzyme Research, Research Associate, 分子酵素学研究センター, 助手 (70284320)
HAYASHI Hideki  The University of Tokushima, Institute for Enzyme Research, Associate Professor, 分子酵素学研究センター, 助教授 (10218589)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 1997: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1996: ¥8,600,000 (Direct Cost: ¥8,600,000)
Keywordsdrug for diabetes / glucose transporter / 糖尿病 / GLUT4トランスロケーション / 非アイソトープ測定 / 三量体Gタンパク
Research Abstract

There are more than 5 million patients of diabetes and a new oral drug must be developed. However, there is not a simple and quantitative method to find the oral diabetic drug. Whole animal was used to find the new drug to estimate the decrease of blood glucose level, but this method is not adeguate toscreen a large number of compound. Translocation of the type 4 glucose transporter (GLUT4) to the cell surface from an intracellular pool is the major mechanism of insulin-stimulated glucose uptake in insulin-target cells. We developed a highly sensitive and quantitative method of detect GLUT4 immunologically on the surface of intact cells, using c-myc epitope-tagged GLUT4 (GLUT4myc). We established stable clones to express GLUT4myc in CHO,L6 myoblasts and 3T3L1 adipocytes. We have developed a simple and new method to screen the compounds for triggering the GLUT4myc translocation in 96 wells using luminessence method. This method is useful for the first screening for developing a new oral drug for diabetes.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Kazuhiro Kishi, Yousuke Ebina, et al.: "Bradykinin directly triggers GLUT4 translocation via an insulin-independent pathway" Diabetes. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nitzan Kozlovsky, Yousuke Ebina, et al.: "Transcriptional activation of the Glutl gene in response to oxidative stress in L6 myotubes" J. Biol. Chem.272. 33367-33372 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Lihong Wang, Yousuke Ebina, et al.: "Hyperinsulinemia but no diabetes in transgenic mice homozygously expressing the tyrosine kinase-deficient human insulin receptor" Biochem. Biophys. res. Commun.240. 446-451 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazuhiko Kishi, Yousuke Ebina, et al.: "Gq-coupled receptors transmit the signal for GLUT4 translocation via an insulin-independent pathway" J. Biol. Chem.271. 26561-26568 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kishi K., Ebina Y.et al.: "Bradykinin directly triggers GLUT4 translocation via an insulin-independent pathway" Diabetes. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kozlovsky N., Ebina Y.et.al.: "Transcriptional activation of the glut1 gene in response to oxidative stress in L6 myotubes" J.Biol.Chem.272. 33367-33372 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Wang L., Ebina Y.et.al.: "Hyperinsulinemia but no diabetes in transgenic mice homozygously expressing the tyrosine kinase-deficient human insulin receptor" biochem.Biophys.Res.Commun. 240. 446-451 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kishi K., Ebina Y.et.al.: "Gq-coupled receptors transmit the signal for GLUT4 translocation via an insulin-independent pathway" J.Biol.Chem.271. 26561-26568 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazuhiro Kishi, Yousuke Ebina, et al.: "Bradykinin directly triggers GLUT4 translocation via an insulin-independent pathway" Diabetes. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Nitzan Kozlovsky, Yousuke Ebina, et al.: "Transcriptional activation of the Glut1 gene in response to oxidative stress in L6 myotubes" J.Biol.Chem.272. 33367-33372 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Lihong Wang, Yousuke Ebina, et al.: "Hyperinsulinemia but no diabetes in transgenic mice homozygously expressing the tyrosine kinase-deficient human insulin receptor" Biochem.Biophys.Res.Commun.240. 446-451 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kazuhiro Kishi, Yousuke Ebina, et al.: "Gq-coupled receptors transmit the signal for GLUT4 translocation via an insulin-independent pathway" J.Biol.Chem.271. 26561-26568 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kishi,K.,Ebina,Y.et al.: "Gq-coupled receptors transmit the signal for GLUT4 translocation via an insulin-independent pathway" J.Biol.Chem.271. 26561-16568 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Todaka,M.,Ebina,Y.et al.: "Roles of insulin, guanosine 5'-[γ-thio]triphosphate and phorbol 12-myristate 13-acetate in signaling pathways of GLUT4 translocation" Biochem.J.315. 875-882 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 蛯名洋介: "化学と生物「インスリンによる細胞内へのグルコース取り込み促進機構」" 日本農芸化学会編集 学会出版センター発行, 2 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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