| Project/Area Number |
16390097
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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, Institute for Enzyme Research, Professor, 分子酵素学研究センター, 教授 (00112227)
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| Co-Investigator(Kenkyū-buntansha) |
OBATA Toshiyuki The University of Tokushima, Institute for Enzyme Research, Associate Professor, 分子酵素学研究センター, 助教授 (40325296)
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)
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)
HOSAKA Toshio The University of Tokushima, Institute for Enzyme Research, Research Associate, 分子酵素学研究センター, 助手 (60403698)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2005: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2004: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | insulin receptor / signal transductor / diabetes / APS / ubiquitination / internalization / 血中遊離インスリン受容体 / 糖毒性 |
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| Research Abstract |
We have shown that serum levels of insulin receptor ectodomain (IRα) are elevated in patients with diabetes mellitus (DM) and shown that the hyperglycemia induced the increase of serum hIRα in newly onset of type 1 DM patients, and a part of IRα bound insulin. Furthermore, we show that the release of IRα is confirmed by diabetic animal model in a glucose concentration-dependent manner. Since we have previously shown that injection of hIRα in mice stimulates an increase in plasma glucose, we are proposing that the increased IRα in patients with DM may take part in the deterioration of glycemic control by sequestering plasma insulin, as one of the factors in glucose toxicity.
APS, a tyrosine kinase adaptor protein with pleckstrin homology and Src homology 2 domains, is rapidly and strongly tyrosine-phosphorylated by insulin receptor kinase upon insulin stimulation. We have previously shown that APS knockout mice have increased insulin-response on adipose tissues. However, the function of APS in insulin signaling has so far been controversial. Here, we report that APS enhanced ligand-dependent multi-ubiquitination of the IR induced enhancement of the IR internalization, but did not affect the IR degradation. This finding shows one of the pleiotropic functions of APS in insulin signaling.
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