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Molecular mechanism underlying the GLUT4 translocation and its abnormality in diabetes mellitus

Research Project

Project/Area Number 12470224
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionThe University of Tokyo

Principal Investigator

ASANO Tomoichiro  Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (70242063)

Co-Investigator(Kenkyū-buntansha) SAKODA Hideyuki  Asahi Life Foundation, Research fellow, 成人病研究所, 研究員
ANAI Motonobu  Asahi Life Foundation, Research fellow, 成人病研究所, 研究員
KATAGIRI Hideki  Faculty of Medicine, Medical Staff, 医学部附属病院, 医員
FUJISHIRO Midori  Faculty of Medicine, Medical Staff, 医学部附属病院, 医員
ONISHI Yukiko  Asahi Life Foundation, Research fellow, 成人病研究所, 研究員
迫田 透之  東京大学, 医学部・附属病院, 医員
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥16,300,000 (Direct Cost: ¥16,300,000)
Fiscal Year 2001: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 2000: ¥10,400,000 (Direct Cost: ¥10,400,000)
KeywordsInsulin / diabetes mellitus / Akt / PI 3 - Kinase / Insulin resistance / 糖輸送担体 / AMPキナーゼ / インスリン作用 / PI3-キナーゼ
Research Abstract

We demonstrated that the activation of PI 3-kinase is necessary for the translocation of GLUT4 to the plasma membrane, and showed that the overexpression of the active mutant of Akt located downstream of PI 3-kinase induced the increased glucose uptake, similarly as observed for insulin stimulation. Since Akt is involved in the insulin-induced glucose metabolisms, we screened the protein associated with Akt, using yeast-two hybrid system, and identified a novel 200kDa protein.
Furthermore, we constructed the system by which we can observe the association of IRS-protein and PI 3-kinase in an intact cell system. On the other hand, we investigated the molecular mechanisms of insulin resistance using various rodent models. An interesting finding is that the insulin-induced PI 3-kinase activation was markedly enhanced in the hypertensive rat models, despite the presence of insulin resistance.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Ono, H., et al.: "Regulation of phosphoinositide metabolism and Akt phosphorylation by PTEN in 3T3-L1 adipocytes"Mol. Endocrinol.. 15. 1411-1422 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujishiro, M., et al.: "MKK6/3 and p38 MAPK pathway activation is not necessary for insulin-induced glucose uptake, but regulates glucose transporter expression"J. Biol. Chem.. 276. 19800-19806 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Oku, A., et al.: "Inhibitory effect of hyperglycemia on insulin-induced Akt/protein kinase B activation in rat skeletal muscle"Am. J. Physiol. Endocrinol. Metab.. 280. E816-E824 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ogihara, T., et al.: "Insulin resistance with enhanced insulin signaling in high-salt diet-fed rats"Diabetes. 50. 573-583 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamada, T., et al.: "3-phosphoinositide-dependent protein kinase 1, an Akt1 kinase, is involved in dephosphorylation of Thr308 of Akt1 in Chinese hamster ovary cells"J. Biol. Chem.. 276. 5339-5345 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sakoda, H., et al.: "Dexamethasone-induced insulin resistance in 3T3-L1 adipocytes is due to inhibition of glucose transport rather than insulin signal transduction"Diabetes. 49. 1700-1708 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Asano, T., et al.: "Abnormal p85/p110 type PI-kinase activation in Zucker fatty rats and high-fat fed rats"Insulin Signaling : From Cultured Cells to Animal Models. 299-320 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ono, H, et al.: "Regulation of phosphoinositide metabolism and Akt phosphotylation by PTEN in 3T3 - L1 adipocyfes"Mol. Endocrinol. 18. 1411-1422 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujishiro, M., et al.: "MKK 6/3 and P38 MAPK pathway activation is not necessary for insulin induces glucose uptake, but regulates glucose transportor expression"J. Biol. Chem.. 276. 19800-19806 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Oku, A., et al.: "Inhibitory effect by hyperglycemia on insulin-induced AKt/protein Kingel B activation in rat skelekl muscle"An. J. Physiol. Endocrinol. Mefab.. 280. E816-E824 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ogihara, T., et al.: "Insulin resistance with enhanced insulin-signaling iu high-salt-Diet-Fed rats"Diabetes. 50. 573-583 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamada, T., et al.: "3-phosphorhositide-dependent protein kinase 1, an Aktl kinase, is involved in dephosphorylation of Thu 308 of AKTl in Chinase hamster ovary cells"J. Biol. Chem.. 276. 5339-5345 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sakoda, H., et al.: "Dexamethasone-induced insulin resistance in 3T3-L3 adipoy〓〓 's due to inhibition of glucose transport rather than insulin signal transduction"Diabetes. 49. 1700-1708 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Asano, T., et al.: "Abnormal p85/p110 type PT-Kinase activation in Zucke〓 fatty rats and high-fal fed rats"Insulin signaling : From Cultured Cells to Animal Models. 299-320 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Conishi, Y., et al.: "Unique Phosphorylation Mechanism of Gab1 Using PI3-kinase"Biochem.Biophys Res Commun.. 288(2). 476-482 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ono, H., et al.: "Regulation of phosphoinositide metabolism and Akt phosphorylation by PTEN in 3T3-L1 adipocytes"Mol.Endocrinol.. 15(8). 1411-1422 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujishiro, M., et al.: "MKK6/3 and p38 MAPK Pathway Activation is not necessary for insulin-induced glucose uptake, but regulates glucose transporter expression"J.Biol.Chem.. 276(23). 19800-19806 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Oku, A., et al.: "Inhibitory effect of hyperglycenia on insulin-induced Akt/protain kinase B activation in rat skeletal muscle"Am.J.Physiol.Endocrinol.Metab.. 280. E816-E824 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ogihara, T., et al.: "Insulin Resistance with Enhanced Insulin-Signaling in High-Salt-Diet-Fed Rats"Diabetes. 50(3). 573-583 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamada, T., et al.: "3-phosphoinositide-dependent protein kinase 1, an Akt1 kinase, is involved in dephosphorylation of Thr308 of Akt1 in Chinese hamster ovary cells"J.Biol.Chem.. 276(7). 5339-5345 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Asano, T., et al.: "Insulin Signaling : From Cultured Cells to Animal Models"Elevier Science Publishers. 22 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sakoda,H.,Ogihara,T., et al.: "Dexamethasone-induced insulin resistance in 3T3-L1 adipocytes is due to inhibition of glucose transport rather than insulin signal transduction"Diabetes. 49(10). 1700-1708 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Asano,T.,Kanda,A., et al.: "P110β is upregulated during differentiation of 373-L cclls cells and contributes to highly insulin-responsive glucose transport activity"J.Biol.Chem.. 275(23). 17671-17676 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Oku,A.,Ueta K., et al.: "Antidiabetic effect of T-1095, an inhibitor of Na^+-glucose cotranspoter,in neonatally streptozotocin-treated rats"Eur.J.Pharm.. 391(1-2). 183-192 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nawano,M.,Oku,A., et al.: "Hyperglycemia enhances insulin resistance in hepatic and adipose tissue,but not skeletal muscle,of ZDF rat."Am.J.Physiol.. 278(3). E535-E543 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fanaki,M.,Katagir,H., et al.: "Structure and function of phophatidylinsitol-3,4 kinase"Cell.Sigual.. 12(3). 135-142 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyazaki,T.,Katagir,H., et al.: "Reciprocal role of ERK and NF-KB pathways in survival and activation of osteoclasts"J.Cell.Biol.. 148(2). 333-342 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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