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2000 Fiscal Year Final Research Report Summary

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

Research Project

Project/Area Number 10557019
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Pathological medical chemistry
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, 分子酵素学研究センター, 研究員
YUASA Tomoyuki  The University of Tokushima, Institute for Enzyme Research, Research Associate, 分子酵素学研究センター, 助手 (50304556)
KISHI Kazuhiro  The University of Tokushima, Institute for Enzyme Research, Associate Professor, 分子酵素学研究センター, 助教授 (70284320)
Project Period (FY) 1998 – 2000
KeywordsType 2 diabetes / Serumsubstance caused for insulin resistance
Research Abstract

NIDDM is primarily caused by the insulin resistance, and increase insulin secretion from pancreatic β-cells and sub-sequently deficiency of insulin. Therefore it is a key to find a substance for insulin resistance in the blood of the patient. There are several substrates in the plasma for insulin resistance, TGF-β, leptin and resistine. However, they are uncertain for insulin resistance of the onset of NIDDM.
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 which is one of the most important physiological effect of insulin. We developed a highly sensitive and quantitative method to detect GLUT4 immunologically on the surface of intact cells, using c-myc epitope-tagged GLUT4 (GLUT4myc). We established stable clones to express GLUT4myc in 3T3L1 adipocytes and established the transgenic rat expressing GLUT4myc in rat adipocytes. We have developed a simple and new method to screen the compounds for triggering the GLUT4myc translocation in 96 wells using luminescence method. This method is useful for the first screening for finding the substances for insulin resistance. Recently, we found a part of known molecule may be the substance for insulin resistance.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Lihong Wang,Yousuke Ebina, et al.: "Gi-mediated translocation of GLUT4 is independent of p85/p110α and p110γ phosphoinositide 3-kinases but might involve the activation of Akt kinase"Biochem.J.. 345. 543-555 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] O.V.Chaika,Yousuke Ebina, et al.: "Mutation of Tyrosine 960 within the Insulin Receptor Juxtamembrane Domain Impairs Glucose Transport but Dose Not Inhibit Ligand-mediated Phosphorylation of Insulin Receptor Substrate-2 in 3T3-L1 Adipocytes"J.Biol.Chem.. 274. 12075-12080 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Lihong Wang,Yousuke Ebina, et al.: "Transient Effect of Platelet-derived Growth Factor (PDGF) on GLUT4 Translocation in 3T3-L1 Adipocytes"J.Biol.Chem.. 274. 19246-19253 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] D.Lauro,Yousuke Ebina, et al.: "Impaired glucose tolerance in mice with a targeted impairment of insulin action in muscle and adipose tissue"Nature Genetics. 20. 294-298 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Imanaka,Yousuke Ebina, et al.: "Reconstitution of Insulin Signaling Pathways in Rat 3Y1 Cells Lacking Insulin Receptor and Insulin Receptor Substrate-1"J.Biol.Chem.. 273. 25347-25355 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuhiro Kishi,Yousuke Ebina, et al.: "Bradykinin directly triggers GLUT4 translocation via an insulin-independent pathway"Diabetes. 47. 550-558 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] L.Wang, Y.Ebina et. al.: "Gi-mediated translocation of GLUT4 is independent of p85/p110α and p110γ phosphoinositide 3-kinases but might involve the activation of Akt kinase"Biochem.J.. 345. 543-555 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] O.V.Chaika, Y.Ebina et. al.: "Mutation of Tyrosine 960 within the Insulin Receptor Juxtamembrane Domain Impairs Glucose Transport but Dose Not Inhibit Ligand-mediated Phosphorylation of Insulin Receptor Substrate-2 in 3T3-L1 Adipocytes"J.Biol.Chem.. 274. 12075-12080 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] L.Wang, Y.Ebina et. al.: "Transient Effect of Platelet-derived Growth Factor (PDGF) on GLUT4 Translocation in 3T3-L1 Adipocytes"J.Biol.Chem.. 274. 19246-19253 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] D.Lauro, Y.Ebina et. al.: "Impaired glucose tolerance in mice with a targeted impairment of insulin action in muscle and adipose tissue"Nature Genetics.. 20. 294-298 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Imanaka, Y.Ebina et. al.: "Reconstitution of Insulin Signaling Pathways in Rat 3Y1 Cells Lacking Insulin Receptor and Insulin Receptor Substrate-1"J.Biol.Chem.. 273. 25347-25355 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Kishi, Y.Ebina et. al.: "Bradykinin directly triggers GLUT4 translocation via an insulin-independent pathway"Diabetes. 47. 550-558 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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