| Project/Area Number |
06404038
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Kobe University |
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Principal Investigator |
KASUGA Masato Kobe University School of Medicine, Professor, 医学部, 教授 (50161047)
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| Co-Investigator(Kenkyū-buntansha) |
MATOZAKI Takashi Kobe University School of Medicine, Assistant Professor, 医学部附属病院, 助手 (80252782)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥29,300,000 (Direct Cost: ¥29,300,000)
Fiscal Year 1995: ¥10,500,000 (Direct Cost: ¥10,500,000)
Fiscal Year 1994: ¥18,800,000 (Direct Cost: ¥18,800,000)
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| Keywords | IRS-1 / PI 3-kinase / Grb2・Sos complex / SH PTP-2 / glucose transporters / Ras / Ras / SH PTP-1 / インスリン |
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| Research Abstract |
Non-insulin-dependent diabetes mellitus (NIDDM) is common disorder of glucose homeostasis affecting -5% of the general population. NIDDM is characterized by defects in the insulin secretion from pancreatic beta-cells and/or the insulin action in peripheral tissues.
Insulin treatment of various intact cells causes rapid tyrosine phosphorylation of a high molecular weight protein (Mr=16,000-185,000) designated pp185. A cDNA encoding pp185 was isolated and the predicted protein was named insulin receptor substrate-1 (IRS-1). Tyrosinphosphorylated IRS-1 binds several signaling molecules, including the 85kDa subunit of phosphoinositide (PI) 3-kinase, Grb2・Sos complex and SH PTP-2 via their Src homology 2 (SH2) domain. To identify new candidate genes for NIDDM,we overexpressed the dominant negative type of 85kDa subunit of PI 3-kinase, Grb2・Sos complex and SH PTP-2 in Chinese hamster ovary cells overexpressing the insulin receptor. Overexpression of dominant negative type of these signaling molecules revealed that PI 3-kinase involves in insulin-stimulated glucose uptake and translocation of glucose transporters, but not in Ras activation. On the other hand, Grb2 and SH PTP-2 involves in insulin-stimulated Ras activation, but not in insulin-stimulated glucose uptake and translocation of glucose transporters. These data suggest that PI 3-kinase is a new candidate gene for NIDDM.
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