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Regulation of insulin-induced metabolic action in whole body by lipid phosphatase

Research Project

Project/Area Number 13671179
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionTOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY

Principal Investigator

SASAOKA Toshiyasu  Toyama Medical & Pharmaceutical Univ. Graduate School of Pharmaceutical Sciences Associate Professor, 大学院・薬学研究科, 助教授 (00272906)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsInuslin / Insulin resistance / Lipid phosphatese / SHIP2 / PI3-kinase / Akt / Atypical PKC / Atypical PKC / リポッドホスファターゼ / atypical PKC
Research Abstract

PI3-kinase product, PI(3,4,5)P3, is a key mediator of insulin-induced metabolic action of insulin. SH2-containing inositol 5'-phosphatase 2 (SHIP2) is a physiologically important lipid phosphatase, which functions to hydrolyze PI(3,4,5)P3 to PI(3,4)P2 in the negative regulation of insulin signaling. We examined whether SHIP2 is associated with the insulin resistance of diabetic db/db mice. The amount of SHIP2 protein was increased in the quadriceps muscle and the epididymal fat tissue, but not in the liver of db/db mice compared to that of control db/+m mice. Insulin-stimulated PI3-kinase activity was modestly decreased in the skeletal muscle, the fat tissue, and the liver of db/db mice compared to that of db/+m mice. In addition to the modest decrease at the level of PI3-kinase, the activity of Akt and atypical PKC, which are downstream molecules of PI3-kinase, was more severely reduced in the skeletal muscle and the fat tissue, but not in the liver, of db/db mice. Treatment with an insulin-sensitizing agent, rosiglitazone, decreased the elevated expression of SHIP2 in the skeletal muscle and the fat tissue of db/db mice. Insulin-induced Akt activation and atypical PKC phosphorylation were restored to the control level, although insulin-stimulated PI3-kinase activation was minimally affected in the skeletal muscle and the fat tissue of db/db mice. These results indicate that SHIP2 is a novel molecule associated with the insulin resistance in the skeletal muscle and the fat tissue, and that insulin-induced activity of the downstream molecules of PI3-kinase is decreased, at least in part, by the elevated expression of SHIP2 in diabetic db/db mice.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Toshiyasu Sasaoka et al.: "SH2-Containing Inositol Phosphatase 2 Negatively Regulates Insulin-Induced Glycogen Synthesis in L6 Myotubes"Diabetologia. Vol.44. 1258-1267 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiroyuki Hori, Toshiyasu Sasaoka, et al.: "Association of SH2-Containing Inositol Phosphatase 2 with the Insulin Resistance of Diabetic db/db Mice"Diabetes. Vol.51. 2387-2394 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hajime Ishihara, Toshiyasu Sasaoka, et al.: "Membrane Localization of Src Homology 2-Containing Inositol 5'-Phosphatase 2 via Shc Assocaition is Required for the Negative Regulation of Insulin Signaling in Rat1 Fibroblasts Overexpressing Insulin Receptors"Molecular Endocrinology. Vol.16. 2371-2381 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshiyasu Sasaoka, Hiroyuki Hori, Manabu Ishiki, Tsutomu Wada, Tetsuro Haruta, Hajime Ishihara, and Masashi Kobayashi.: "SH2-containing inositol phosphatase 2 negatively regulates insulin-induced glycogen synthesis in L6 myotubes."Diabetologia. 44. 1258-1267 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiroyuki Hori, Toshiyasu Sasaoka, Hajime Ishihara, Tsutomu Wada, Shihou Murakami, Manabu Ishiki, and Masashi Kobayashi.: "Association of SH2-containing inositol phosphatase 2 with the insulin resistance of diabetic db/db mice."Diabetes. 51. 2387-2394 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hajime Ishihara, Toshiyasu Sasaoka, Manabu Ishiki, Tsutomu Wada, Hiroyuki Hori, Syota Kagawa, and Masashi Kobayashi.: "Membrane localization of Src homology 2-containing inositol 5-phosphatse 2 via Shc association is required for the negative regulation of insulin signaling in Rat1 fibroblasts overexpressing insulin receptors."Molecular Endocrinology. 16. 2371-2381 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiroyuki Hori, Toshiyasu Sasaoka, et al.: "Association of SH2-Containing Inositol Phosphatase 2 with the Insulin Resistance of Diabetic db/db Mice"Diabetes. 51. 2387-2394 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hajime Ishihara, Toshiyasu Sasaoka, et al.: "Membrane Localization of Src Homology 2-Containing Inositol 5'-Phosphatase 2 via Shc Association is Required for the Negative Regulation of Insulin Signaling in Rat1 Fibroblasts Overexpressing Insulin Receptors"Molecular Endocrinology. 16. 2371-2381 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsutomu Wada, Toshiyasu Sasaoka et al.: "Overexpression of SH2-Containing Inositol Phosphatase 2Results in Negative Regulation of Insulin-Induced Metabolic Actions in 3T3-L1 Adipocytes via Its 5'-Phosphatase Catalytic Activity"Molecular and Cellular Biology. 21-5. 1633-1646 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Toshiyasu Sasaoka et al.: "SH2-containing inositol phosphatase 2 negatively regulates Insulin-induced glycogen synthesis in L6 myotubes"Diabetologia. 44. 1258-1267 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Toshiyasu Sasaoka et al.: "Tyrosine Phosphorylation-Dependent and -Independent Role of She in the Regulation of IGF-1-Induced Mitogenesis and Glycogen Synthesis"Endocrinoligy. 142-12. 5226-5235 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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