MECHANISMS FOR INSULIN RESISTANCE BY SERINE KINASE ACTIVATION
| Project/Area Number |
17590918
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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 |
Metabolomics
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| Research Institution | University of Toyama |
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Principal Investigator |
KOBAYASHI Masashi University of Toyama, Department of Medicine, Exctive Vice President and Director of University Hospital, 事務局・理事(副学長)病院長 (80115758)
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| Co-Investigator(Kenkyū-buntansha) |
USUI Isao University of Toyama, University Hospital, Assistant Professor, 附属病院, 助手 (50377272)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | insulin resistance / IRS-1 / serine phosphorylation / serine kinase / JNK / mTOR |
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| Research Abstract |
We investigated the mechanisms for insulin resistance associated to the activation of several serine kinases. First project was the analysis of the new serine kinases. We found that p70S6 kinase was involved in the serine phosphorylation of IRS-1 after TNFa stimulation. Mdm2 was a ubiquitin ligase, which ubiquitinated IRS-1 after insulin stimulation in PI3-kinase dependent manner. These data were deported in the annual meeting of Japan Diabetes Association. Second project was about the new ligands, which stimulated IRS-1 serine phosphorylation. We found that IL-la stimulated several serine kinases, in which JNK and mTOR were important for IRS-1 serine phosphorylation. These data were reported in Molecular Endocrinology. Then, the different mechanisms for IRS-1 serine phosphorylation by either anisomycin or insulin were studied. JNK was important for the former, whereas mTOR was important for the latter. These data were reported in BBRC. The third project was the evaluation of IRS-1 serine phosphorylation and SOCS expression, both of which were known to be important for the degradation of IRS-1, in in vivo insulin resistant models. In high fat-fed mice and db/db/ mice, IRS-1 serine phosphorylation and SOCS expression was enhanced. Pioglitazone, a insulin sensitizing drug, decreased both IRS-1 serine phyosphorylation and SOCS expression, leading to the enhanced insulin signaling at IRS-1 level. These data were reported in Diabetes. Finally, the relationship between IRS-1 serine phosphorylation and SOCS expression was examined. We found that insulin signaling was inhibited in the presence of both IRS-1 serine phosphorylation and SOCS expression, one of which did not induce insulin resistance in 3T3-L1 adipocytes. These data were reported in Endocrinology.
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Report
(3 results)
Research Products
(10 results)
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[Journal Article] Chronic TNF {alpha} Treatment Causes Insulin Resistance via IRS-1 Serine Phosphorylation and SOCS3 Induction in 3T3-L1 Adipocytes.2007
Author(s)
Ishizuka K, Usui I, Kanatani Y, Bukhari A, He J, Fujisaka S, Yamazald Y, Suzuki H, Hiratani K, Ishiki M, Iwata M, Urakaze M, Haruta T, Kobayashi M.
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Journal Title
Endocrinology. (In press)
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Chronic TNF {alpha} Treatment Causes Insulin Resistance via IRS-1 Serine Phosphorylation and SOCS3 Induction in 3T3-L1 Adipocytes.2007
Author(s)
Ishizuka K, Usui I, Kanatani Y, Bukhari A, He J, Fujisaka S, Yamazaki Y, Suzuki H, Hiratani K, Ishiki M, Iwata M, Urakaze Haruta T, Kobayashi M
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Journal Title
Description
「研究成果報告書概要(欧文)」より
Related Report
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