| Project/Area Number |
15081206
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyoto University |
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Principal Investigator |
HORIUCHI Hisanori Kyoto University, Graduate School of Medicine, Associate Professor (90291426)
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| Co-Investigator(Kenkyū-buntansha) |
ONO Koh Kyoto University, Graduate School of Medicine, Assistant Professor (00359275)
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| Project Period (FY) |
2003 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥38,400,000 (Direct Cost: ¥38,400,000)
Fiscal Year 2007: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2006: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2005: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 2004: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 2003: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | adipocytes / Ral / GLUT4 / gene trap / adiponectin / AMPK / exocyst complex / GAP / インスリン / 開口放出 / streptolysin-O / 脂肪滴 / 分化因子 / Rab / adiponectin / lipolysis / Munc13-4 / グルコーストランスポータ4 / エクソサイトーシス / ストレプトライシン-O / Rab27 |
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| Research Abstract |
By exocytosis, adipocytes release adiponectin and increase of surface expression of glucose transporter-4 (GLUT4) molecules. We have developed assays for evaluating GLUT4 translocation in 3T3 adipocytes and cardiac muscle cells and found that H_2O_2, an oxidative stress, induced GLUT4 translocation via AMP-dependent protein kinase (AMPK) pathway in cardiac muscle cells. The small GTPase Ral have been demonstrated to play an important role in the regulation of GLUT4 translocation in adipocytes. We have demonstarated that Ral regulates the granule secretion via its effector, the exocyst tethering factor complex, by enhancing the calcium-ion sensitivity of the exocytosis in our established granule secretion assay using permeabilized platelets. We then identified Ral GAPs, the inhibitory regulators for Ral, for the first time. We have generated mice lacking Ral GAPs. We are investigating their adipose tissue structures and their serum glucose levels in response to insulin. On the other hand, we have established a gene trap method for identification of adipocyte differentiation factors using retrovirus insertion-mediated random mutagenesis. With the method, we have identified several molecules including TG-interacting factor and enkepharin. Hypoadiponectinemia is a risk of atherosclerotic diseases. We have found that serum adiponectin levels are associated with higher motality in chronic heart failure patients.
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