| Project/Area Number |
05044171
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Kobe University |
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Principal Investigator |
KASUGA Masato Kobe University School of Medicine, Professer, 医学部, 教授 (50161047)
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| Co-Investigator(Kenkyū-buntansha) |
HOLMAN Geoffrey d. The University of Bath The School of Biology, Reader in Biochemistry, 生物学部, 講師
WATERFIELD M ルードウィヒン癌研究所, 所長
YOKONO Kouichi Kobe University School of Medicine, Reader in Biochemistry, 医学部・府属病院, 講師 (50144580)
WATERFIELD Michel d. Ludwig Institute for Cancer Resarch, Director of Rescarch
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 1994: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1993: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | Insulin / GLUT / PI 3-kinase / 膜ラッフル形成 |
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| Research Abstract |
In collaboration with Professor M.Waterfield in London, we found phosphoinositide 3-kinases associated with IRS-1 mediate the stimulatory effect of insulin on the glucose transport (translocation of glucose transporters) and membrane ruffling. We also found that an adaptor protein Nck, which binds to IRS-1, associates two proteins of 116kDa and 130kDa in vitro. The amino acid sequence of these proteins was analyzed in Professor Waterfield's laboratory and we cloned the cDNA of these two proteins.
In collaboration with Professor G.Holman in Bath, we found that wortmannin, an inhibitor of phosphoinositide 3-kinase, inhibits the stimulatory effect of insulin on glucose transport (translocation of GLUT4 from cytosols to plasma membranes) in 3T3-L1 adipocytes. Furthermore, we analyzed the kinetics of GLUT4 in the presence of wortmannin and insulin and concluded that wortmannin inhibited the stimulatory effect of insulin on the exocytosis, but not the endocytosis, of GULT4 in 3T3-L1 adipocytes.
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