| Project/Area Number |
20390095
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
EBINA Yousuke The University of Tokushima, 疾患酵素学研究センター, 教授 (00112227)
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| Co-Investigator(Renkei-kenkyūsha) |
UCHIYAMA Keiji 徳島大学, 疾患酵素学研究センター, 准教授 (60294039)
YUASA Tomoyuki 徳島大学, 疾患酵素学研究センター, 准教授 (50304556)
NAGAYA Hisao 徳島大学, 疾患酵素学研究センター, 助教 (60464343)
OGURA Yuko 徳島大学, 疾患酵素学研究センター, 研究員 (90464354)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Fiscal Year 2010: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2008: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | 分子病態学 / インスリンシグナル伝達 / インスリン作用 / GLUT4 / TUG / sIR / 高血糖 / 超高感度sIR測定法 / シグナル伝達 / BFA / GLUT4トランスロケーション / ARF / BIG2 |
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| Research Abstract |
Akt substrate of 160kDa (AS160) is a Rab GTPase activating protein (GAP) and was recently identified as a component of the insulin signaling pathway of glucose transporter type 4 (GLUT4) translocation. We and others, previously reported that the activation of Galphaq protein-coupled receptors (GalphaqPCRs) also stimulated GLUT4 translocation and glucose uptake in several cell lines. Here, we report that the activation of GalphaqPCRs also promoted phosphorylation of AS160 by the 5'-AMP activated proteinkinase (AMPK). Rat 3Y1 cells lacking AS160 did not show insulin-induced GLUT4 translocation. The cells stably expressing GLUT4 revealed GLUT4 vesicles that were mainly localized in the perinuclear region and less frequently on the cell surface. After expression of exogenous AS160, GLUT4 on the cell surface decreased and GLUT4 vesicles were redistributed throughout the cytoplasm. Although PMA-induced or sodium fluoride-induced GLUT4 translocation was significantly increased in these cells, insulin did not affect GLUT4 translocation. These results suggest that AS160 is a common regulator of insulin-and GalphaqPCR activation-mediated GLUT4 distribution in the cells.
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