• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Roles of stimulatory and inhibitory protein-tyrosine phosphatase in pathogenesis of insulin resistance

Research Project

Project/Area Number 08671148
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionShiga University of Medical Science

Principal Investigator

MAEGAWA Hiroshi  Shiga University of Medical Science Faculty of Medicine, Assistant Professor, 医学部, 助手 (00209363)

Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsPTPase / SHP-2 / Janus kinase 2 / Trasgenic mice / Insulin resistance / Crk-associated substrate / SHP-2 / Janus kinase 2 (JAK2) / SHPTP2
Research Abstract

To clarify the roles of protein-tyrosine phosphatase (PTPase) in pathogenesis of insulin resistance, we first investigated insulin signal and insulin action in the cells cultured in high glucose condition, because several species of PTPase (PTP1B,LAR and LRP) were activated in the high-glucose condition, and we found that and insulin signal transduction was attenuated, resulting in insulin resistance. Furthermore, overeexpression of PTP1B,one of the cytosolic PTPase led to attenuated insulin signal transduction. Thus, these PTPase seem to be negative regulator of insulin signal transduction. One the other hand, SHP-2 was a unique PTPase containing Src homology 2 regions on its N-terminus, and the introduction of a dominant negative SHP-2 inhibited insulin signal transduction. Thus, this PTPase is considered to be a positive regulator of insulin signal transduction. Furthermore, we found this SHP-2 interacted with Janus kinase 2 and Crk-associated substrate, and SHP-2 might regulate their functions. Finally, we made transgenic mice expressing our dominant negative SHP-2, and these mice showed insulin resistance. Now, we are studying the mechanism of insulin resistance in these Tg mice.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Ugi S, Maegawa H et al.: "Expression of dominant negative mutant SHPTP2 attenuates phosphatidylinositol 3'-kinase activity via modulation of phosphorylation of insulin receptor substrate-1" J Biol Chem. 271. 12595-12602 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Obata T, Kashiwagi A, Maegawa H et al.: "Insulin-signaling and its regulation of system A amino acid uptake in cultured rat vascular smooth muscles cells." Circulation Research. 79. 1167-1176 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Maegawa H et al.: "SHPTP2 serves adapter protein linking between Janus kinase 2 and insulin receptor substrates" Biochem Biophys Res Commun. 228. 122-127 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Obata T, Maegawa H et al.: "High-glucose induced abnormal epidermal growth factor signaling" J.Biochem,Tokyo. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 長谷川、前川他: "Dominant negative SHPTP2トランスジエニックマウスの作成" 糖尿病. 40. 115-122 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 長谷川、前川 他: "Dominant negative SHP2発現トランスジェニックマウスにおけるインスリン抵抗性の分子機構" 分子糖尿病学. 8. 131-135 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ugi S,Maegawa H,Kashiwagi A,Adachi M,Olefsky JM and Kikkawa R.: "Expression of dominant negative mutant SHPTP2 attenuates phosphatidylinositol 3'-kinase activity via modulation of phosphorylation of insulin receptor substrate-1." J.Biol.Chem.271. 12595-12602 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Obata T,Kashiwagi A,Maegawa H,Nishio Y,Ugi S,Hidaka H,Kikkawa R.: "Insulin-signaling and its regulation of system A amino acid uptake in cultured rat vascular smooth muscles cells." Circulation Research. 79. 1167-1176 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Maegawa H,Kashiwagi A,Fujita T,Ugi S,Hasegawa M,Obata T,Nishio Y,Kojima H,Hidaka H and Kikkawa R.: "SHPTP2 serves adapter protein linking between Janus kinase 2 and insulin receptor substrates" Biochem Biophys Res.Commun. 228. 122-127 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hasegawa M,Maegawa H,Sugai S,Sakamoto T.Kitagawa K,Tajima H,Ugi S,Fujita T,Obata T and Kikkawa R.: "Expression of a dominant negative SHPTP2 in transgenic mice induces insulin resistance." Diabetes 45. S1. 50A (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujita T,Maegawa H,Obata T,Hidaka H,Kikkawa R.: "Insulin induces dephosphorylation of Crk-associated substrate." Diabetes 46. S1. 284A (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Obata T,Maegawa H,Fujita T,Shibata T,Kashiwagi A,Kikkawa R.: "A new antidiabetic agent (JTT-501) acutely stimulates glucose disposal rates by enhancing insulin signal transduction." Diabetes 46. S1. 203A (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Obata T,Maegawa H,Kashiwagi A,Pillay Ts , Kikkawa R.: "High-glucose induced abnormal Epidermal growth factor signaling." J.Biochem, Tokyo. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujita T, Maegawa H et al.: "Insulin induces dephosphaoryaltion of Crk-associated substrate" Diabetes. 46,S1. 284A (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Obata T, Maegawa H et al.: "A new antidiabetic agent (JTT-501) acutely stimulates glucose disposal rates by enhancing insulin signal transduction" Diabetes. 46,S1. 203A (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 長谷川, 前川 他: "Dominant negative SHPTP2トランスジェニックマウスの作成" 糖尿病. 40. 115-122 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 長谷川, 前川 他: "Dominant negative SHP2発現トランスジェニックマウスにおけるインスリン抵抗性の分子機構" 分子糖尿病学. 8. 131-135 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Obata T, Maegawa H et al.: "High-glucose-induced abnormal Epidermal growth factor signaling." J.Biochem.Tokyo. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Ugi S,Maegawa H et al.: "Expression of dominant negative mutant SHPTP2 attenuates phosphatidylinositol 3′-kinase activity via modulation of phosphorylation of insulin receptor substrate-1" J Biol Chem. 271. 12595-12602 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Obata T,Kashiwagi A,Maegawa H et al.: "Insulin-signaling and its regulation of system A amino acid uptake in cultured rat vascular smooth muscles cells." Circulation Research. 79. 1167-1176 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Maegawa H et al.: "SHPTP2 serves adapter protein linking between Janus kinase 2 and insulin receptor substrates" Biochem Biophys Res Commun. 228. 122-127 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hasegawa M,Maegawa H et al.: "Expression of a dominant negative SHPTP2 in transgenic mice induces insulin resistance." Diabetes. 45,S1. 50A- (1996)

    • Related Report
      1996 Annual Research Report

URL: 

Published: 1996-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi