| Project/Area Number |
09671021
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Gunma University, Institute For Molecular and Cellular Regulation |
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Principal Investigator |
SHIBATA Hiroshi Institute for Molecular and Cellular Regulation, Department of Cell Biology, Associate Professor, 生体調節研究所, 助教授 (20235584)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | insulin / glucose transporter / GTP-binding protein / Rab4 / syntaxin4 / dynamin / グリコーストランスポーター |
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| Research Abstract |
In the present study, we calrified that insulin stimulated guanine nucleotide exchange on Rab4 in rat adipocytes. This insulin action was markedly attenuated with phosphatidylinositol (PI) 3-kinase inhibitors, wortmannin or LY294002, suggesting that Pl 3-kinase may be an essential signaling component for insulin activation of Rab4. Additionally, we investigated the interaction of Rab4 with syntaxin4, a t-SNARE protein implicated in the insulin-induced exocytic fusion of the GLUT4-containing vesicle with the plasma membrane. Rab4 and syntaxin4 were co-immunoprecipitated from the homogenate of rat adipocytes. The interaction of the two proteins were attenuated by pretreatment of the cells with insulin but enhanced with GTPgammaS.GTP-binding proteins regulate both exocytotic and endocytotic steps of GLUT4-containing vesicles in rat adipocytes. Furthermore, we demonstrated that protein kinase Cgamma may be the upstream regulator of the insulin action on Rab4.
We also clarified that dynamin is a regulatory GTPase of GLUT4 endocytosis by using mutant dynamin expressed in CHO cells.
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