Molecular mechanisms of glucose uptake by insulin-independent pathway
| Project/Area Number |
13670144
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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 |
Pathological medical chemistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KISHI Kazuhiro The University of Tokushima, Institute for Enzyme Research, Associate Professor, 分子酵素学研究センター, 助教授 (70284320)
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| Co-Investigator(Kenkyū-buntansha) |
YUASA Tomoyuki The University of Tokushima, Institute for Enzyme Research, Research Associate, 分子酵素学研究センター, 助手 (50304556)
EBINA Yousuke The University of Tokushima, Institute for Enzyme Research, Professor, 分子酵素学研究センター, 教授 (00112227)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | APS / carbobydrate metabolism / APS knockout mouse / insulin resistance / GLUT4トランスロケーション / グルコース取り込み / Gq |
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| Research Abstract |
APS, a tyrosine kinase adaptor protein containing pleckstrin homology and Src homology 2 domains, is rapidly and strongly tyrosine-phosphrylated by insulin receptor kinase upon insulin stimulation. The function of APS in insulin signaling has heretofore remained unknown. To investigate its function in vivo, APS-deficient (-/-) mice were employed. The blood glucose-lowering effect of insulin, as assessed by the intraperitoneal insulin tolerance test, was increased in APS-/- mice. Plasma insulin levels during fasting and in the intraperitoneal glucose tolerance test were lower in APS-/- mice. APS-/- mice showed an increase in the whole-body glucose infusion rate as assessed by the hyperinsulinemic euglycemic clamp test. These findings indicated that APS-/- mice exhibited increased sensitivity to insulin. However, overexpression of wild-type or dominant negative APS in 3T3L1 adipocytes and Chinese hamster ovary cells did not affect ins! Ulin receptor numbers, phosphoryla tions of insulin receptor, insulin receptor substrate-1, Akt and MAP kinase. The glucose uptake and GLUT4 translocation were not affected by insulin stimulation in these cells. Nevertheless, the insulin-stimulated glucose transport in isolated adipocytes of APS-/- mice was increased over that of APS+/+ mice. APS-/- mice also showed increased serum levels of leptin and adiponectin, which might explain the increased insulin sensitivity of adiposytes.
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Report
(3 results)
Research Products
(3 results)
