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MECHANISM OF INSULIN SIGNAL ON GLUCOSE TRANSPORT IN KNOCKOUT MICE

Research Project

Project/Area Number 07671148
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 InstitutionYokohama City University Hospital

Principal Investigator

SATOH Shinobu  Yokohama City University Hospital, Assistant Professor, 医学部・付属病院, 講師 (80244424)

Co-Investigator(Kenkyū-buntansha) ITO Takaaki  School of Medicine, Yokohama City University Hospital, Associate Professor, 医学部, 助教授 (70168392)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsinsulin / glucose transport / glucose transporter / GLUT4 / IRS-1 / knockout mice / PI 3-kinase / pp60 / PI-3 kinase / p6c
Research Abstract

In adipose and muscle tissue, the major targets of insulin-induced glucose transport, it is known that glucose transporter isoform GLUT4 translocates from a large intracellular pool to the cell surface in response to insulin, although the signaling mechanism regulating this process is not fully understood. Insulin enhances tyrosine phosphorylation of several endogenous substrates such as insulin receptor substrate (IRS)-1, IRS-2, Grb2-associated binder-1 (GRB1) and Shc. Phosphatidylinositol (PI) 3-kinase play the important role for insulin signal transduction on glucose transport. Insulin is thought to activated this enzyme via binding to phosphotyrosine-containing proteins such as IRS-1 and IRS-2 and pp60. To investigate the relationship between endogenous substrates and glucose transport in adipose cells, we analyzed mice with targeted disruption of the endogenous substrate gene, IRS-1. Insulin-stimulated PI 3-kinase activity in the antiphosphotyrosine immnoprecipitates is 54.3 % of wild type in adipose cells from the mice. Pp60 was the major tyrosine phosphorylated protein and predominantly associated with PI 3-kinase, whereas tyrosine phosphorylation of IRS-2 and its association with this enzyme are very low. In these cells, glucose transport, glucose transport and GLUT4 translocation are decreased to 52 % and 67.9 % of those from wild-type, respectively, sensitivity of insulin to stimulate glucose transport was also impaired. These data suggested that 1) IRS-1 plays a major role in insuln-induced translocation of GLUT4 in adipose cells from wild-type mice, and 2) pp60 takes in this process via activation of PI 3-kinase in the absence of IRS-1.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Kono-Sugita,Eri: "Insulin-induced GLUT4 recycling in rat adipose cells by a pathway insensidive to brefeldin A" European Journal of Biochemistry. 236. 1033-1037 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sato,Yasushi: "Immunohistochemical localization of facilitated distusion glucose transporless in rat pancreatie islets" Tissue and Cell. 28. 637-643 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kadowaki,Takashi: "Insulin resistance and grauth retardation in mice lacking insulin receptor substratel and identification of insulin receptor substrak 2" Diabetic Medicine. 13. S103-S108 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kawano,Naomi: "Immunoexpression of the α subunit of a guanire nucleotide-binding protein(Go)in pulmanary reuroendocrine cell and neoplasms" Pathology International. 46. 393-398 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ito,Takaaki: "Pulmarary endocrine cell hyperplasia and papillona in rats induced by intratracheal injection of extract from puticular air pollutant" Experimental and Toxicologic Pathology. 49(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Udaka,Naoko: "Expression of connexin 32 gap junction protein in the kidneys during fetal development of the hamster(Mesocricetus auratus)" Anat.Embryol. 192. 399-406 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 佐藤忍: "シグナル伝達実験法(分担)" 宇井理生編 羊土社 東京, 267(86-92) (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 佐藤忍: "糖尿病研究ストラテジー" 清野進,岡芳知編 秀潤社 東京, 417(306-310) (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sugita-Kono E,Satoh S,Suzuki Y,Egawa M,Udaka N,Ito T,Sekihara H: "Insulin-induced GLUT4 recycling in rat adipose cells by a pathway insensitive to Brefeldin A" Eur.J.Biochem.236 (3). 1033-1037 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sato Y,Ito T,Udaka N,Kanisawa M,Noguchi Y,Cushman S W,Satoh S: "Immunohistchemical localization of dacilitated-difusion glucose transporter in rat pancreatic islets" Tissue and Cell. 28 (6). 637-643 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kadowaki T,Tamemoto H,Tobe K,Terauch Y,Ueki K,Kaburagi Y,Yamauchi T,Satoh S,Sekihara H,Aizawa S,Yazaki Y: "Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1 and indentification of insulin receptor substrate-2" Diabetic Medicine. 13 (9). S103-S108 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ito T,Ohyama K,Kusano T,Usuda Y,Nozawa A,Hayashi H,Ohji H,Kitamura H,Kanisawa M: "Plumonary endocrine cell hyperplasia and papilloma in rats induced by intratrachal injection of extrzct from particulate air pollutants" Experimental and Toxicilogic Pathology. 49 (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Udaka N,Ito T,Sato Y,Satoh S,Kanisawa M: "Expression of connexin 32gap junction protein in the kidneys during fetal development of the hamster (mesocricetus auratus)" Anat Embryol. 192. 399-406 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kono-Sugita,Eri: "Insulin-induced GLUT4 recycling in rat adipose cells by a pathway insensitive to brefeldin A" European Journal of Biochemistry. 236・3. 1033-1037 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sato,Yasushi: "Immunohistochemical localization of dacilitared diffusion glucose transporters in rat pancreatic islets" Tissue and Cell. 28・6. 637-643 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kadowaki,Takashi: "Insulin resistance and growth retardation in mice cadoing insulin receptor substrate and identification insulin receptor substrate 2" Diabetic Medicine. 13・6. s103-s108 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kawano,Naomi: "Immunoexpression of the α subunit of a guanire nucleotide-binding protein (Go) in pulmonary neuroendocrine cells and neoplisms" Pathology International. 46・5. 393-398 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ito,Takaaki: "Pulmonaty endocrine cell hyperplasia and papilloma in rats induced by intrutrucheol injection of extract from particulate wr pallutonls" Experimental and Toxicologic Pathology. 49(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] 佐藤忍: "シグナル伝達実験法(分担)" 宇井理性論 羊土社,東京, 267(86-92) (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Eri Kono-Sugita: "Insulin-induced GLUT4 recycling in rat adipose cells by a pathway in sensitive to brefeldin A" European Journal of Biochemistry. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Naoko Udaka: "Expression of connexin 32 gap junction protein in the kidneys during fetal development of the hamster" Anat Embryol. 192. 399-406 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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