2004 Fiscal Year Final Research Report Summary
Analysis of negative-feed back mechanism through mTOR pathway in insulin action.
| Project/Area Number |
15590932
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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 | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
KOBAYASHI Masashi Toyama Medical and Pharmaceutical University, Faculty of Medicine, Professor, 医学部, 教授 (80115758)
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| Project Period (FY) |
2003 – 2004
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| Keywords | IRS-1 / serine kinase / JNK / IL-1 / IKK / proteasome |
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| Research Abstract |
1)Roles of mTOR and INK in insulin or anisomycin-induced IRS-1 serine phosphorylation.
In 3T3-L1 adipocytes, insulin-induced phosphorylation of IRS-1 on Ser 307, ser 612, and Ser 636/639 was reduced by rapamycin, and was further inhibited by the combination with JNK inhibitor, SP 600125. Anisomycin-induced phosphorylation on the same residues was inhibited both rapamycin and SP 600125. Unlike insulin, anisomycin failed to elicit translocation or degradation of IRS-1. Therefore, mTOR and JNK pathways play the same IRS-1 serine phosphorylation, but are different in IRS-1 translocation and degradation.
2)IL-1α and IRS-1 serine phosphorylation.
IRS-1 was transiently phosphorylated on some serine residues around 15min after IL-1 stimulation, when several serine kinases, IKK, JNK, ERK, and p70S6K were activated. Tyrosine phosphorylation of IRS-1 was recovered only by IKK inhibitor or JNK inhibotor, suggesting the specific involvement of these two kinases. Insulin-stimulated Akt phosphorylation and 2-deoxyglucose uptake were not inhibited by IL-1. Akt phosphorylation was synergistically inhibited by IL-1 in the presence IL-6. Thus, short term IL-1 treatment transiently causes insulin resistance at the level of IRS-1 with its serine phosphorylation. IL1 may suppress insulin signaling downstream of IRS-1 in the presence of other cytokines, such as IL-6.
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Research Products
(18 results)
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[Journal Article] SH2-containing inositol phosphatase 2 predominantly regulates Akt2, and not Akt1, phosphorylation at the plasma membrane in response to insulin in 3T3-L1 adipocytes.2004
Author(s)
Sasaoka T., Wada T., Fukui K., Murakami S., Ishihara H., Suzuki R., Tobe K., Kadowaki T., Kobayashi M.
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Journal Title
J Biol Chem 279
Pages: 14835-14843
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Association of the polymorphisms in the 5'-untranslated region of PTEN gene with type 2 diabetes in a Japanese population.2003
Author(s)
Ishihara H., Sasaoka T., Kagawa S., Murakami S., Fukui K., Kawagishi Y., Yamazaki K., Sato A., Iwata M., Urakaze M., Ishiki M., Wada T., Yaguchi S., Tsuneki H., Kimura I., Kobayashi M.
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Journal Title
FEBS Lett. 554
Pages: 450-454
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Dual role of src homology domain 2-containing inositol phosphatase 2 in the regulation of platelet-derived growth factor and insulin-like growth factor 1 signaling in rat vascular smooth muscle cells.2003
Author(s)
Sasaoka T., Kikuchi K., Wada T., Sato A., Hori H., Murakami S., Fukui K., Ishihara H., Aota R., Kimura I., Kobayashi M.
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Journal Title
Endocrinology 144
Pages: 4204-4214
Description
「研究成果報告書概要(欧文)」より
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