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

Molecular mechanisms of insulin signal transduction and diabetes mellitus

Research Project

Project/Area Number 18390104
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionThe University of Tokushima

Principal Investigator

EBINA Yousuke  The University of Tokushima, Institute for Enzyme Research, Professor (00112227)

Co-Investigator(Kenkyū-buntansha) UCHIYAMA Keiji  The University of Tokushima, Institute for Enzyme Research, Associate Professor (60294039)
YUASA Tomoyuki  The University of Tokushima, Institute for Enzyme Research, Assistant Professor (50304556)
NAGAYA Hisao  The University of Tokushima, Institute for Enzyme Research, Assistant Professor (60464343)
OGURA Yuko  The University of Tokushima, Institute for Enzyme Research, COE Researcher (90464354)
小畑 利之  徳島大学, 分子酵素学研究センター, 助教授 (40325296)
勅使河原 匡  徳島大学, 分子酵素学研究センター, COE研究員 (40403737)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥16,830,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2007: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2006: ¥7,600,000 (Direct Cost: ¥7,600,000)
Keywordsinsulin receptor / soluble ectodomain / diabetes / signal transduction / GLUT4 translocation / AS160 / Gq coupled receptor / インスリン
Research Abstract

The ectodomains of receptors for several cytokines and growth factors have been found to circulate in plasma. Thus, the existence of soluble IR in human serum has been suspected.
Furthermore, transgenic mice secreting soluble IRα into the plasma showed chronic hyperglycemia. Here, we established novel enzyme-linked immunosorbent assay (ELISA) systems to measure both the ectodomain (α-subunit and a part of β-subunit) of IR and full length of IR.
With these ELISA systems, we report that soluble hlRα with parts of extracellular region of hIRβ, but not as a whole IR or with intact hlRβ, is present in human plasma and that its plasma level is elevated in patients with elevated blood glucose. The ectodomain of IR may be cleaved, at least in part, by hyperglycemic state-associated mechanisms.
We and others previously reported that the activation of Gaq protein- coupled receptors (GaqPCRs) also stimulates GLUT4 translocation and glucose uptake in several cell lines. Here, we report that the activation of GaqPCRs also promoted the phosphorylation of AS160, Akt substrate of 160 KDa which is Rab GTPase activating protein (GAP), by 5'-AMP activated protein kinase (AMPK). The suppression of AS160 phosphorylation by AMPKα1 subunit knockdown using siRNA promoted GLUT4 vesicle retention at intracellular compartments, but did not affect a fold increase of the Gaq- stimulated GLUT4 translocation. These results suggest that AS160 is a common mediator of the GLUT4 vesicle trafficking stimulated by insulin and by the activation of GaqPCR. The AS160 regulates the intracellular distribution of the GLUT4 vesicles and its retention inside the cells.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (13 results)

All 2008 2007

All Journal Article (13 results) (of which Peer Reviewed: 6 results)

  • [Journal Article] IRS I -Independent Defects Define Major Nodes of Insulin Resistance2008

    • Author(s)
      Hoehn, KL., et. al.
    • Journal Title

      Cell Metabolism 7

      Pages: 421-433

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] APS-mediated Ubiquitination of the Insulin Receptor Enhances its Internalization, but does not Induce its Degradation.2007

    • Author(s)
      Kishi K.
    • Journal Title

      Endocrine Journal 54

      Pages: 77-88

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Angiotensin II inhibits insulin-induced actin stress fiber formation and glucose uptake via ERK1/22007

    • Author(s)
      Nazari H.
    • Journal Title

      The Journal of Medical Investigation 54

      Pages: 19-27

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Deficiency of Cbl-b gene enhances infiltration and activation of macrophages in adipose tissue and causes peripheral insulin resistance in mice2007

    • Author(s)
      Hirasaka K.
    • Journal Title

      Diabetes 56

      Pages: 2511-2522

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Soluble insulin receptor ectodomain is elevated in the plasma of patients with diabetes mellitus.2007

    • Author(s)
      Obata T.
    • Journal Title

      Diabetes 56

      Pages: 2028-2035

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] APS-mediated Ubiquitination of the Insulin Receptor Enhances its Internalization, but does not Induce its Degradation2007

    • Author(s)
      Kishi, K., et. al.
    • Journal Title

      Endocrine Journal 54

      Pages: 77-88

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Angiotensin II inhibits insulin-induced actin stress fiber formation and glucose uptake via ERK1/22007

    • Author(s)
      Nazari, H., et. al.
    • Journal Title

      The Journal of Medical Investigation 54

      Pages: 19-27

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Deficiency of Cbl-b gene enhances infiltration and activation of macrophages in adipose tissue and causes peripheral insulin resistance in mice2007

    • Author(s)
      Hirasaka, K., et. al.
    • Journal Title

      Diabetes 56

      Pages: 2511-2522

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Soluble insulin receptor ectodomain is elevated in the plasma of patients with diabetes mellitus2007

    • Author(s)
      Obata, T., et. al.
    • Journal Title

      Diabetes 56

      Pages: 2028-2035

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Deficiency of Cbl-b gene enhances infiltration and activation of macrophages in adipose tissue and causes peripheral insulin resistance in mice2007

    • Author(s)
      Katsuya Hirasaka
    • Journal Title

      Diabetes 56

      Pages: 2511-2522

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Soluble insulin receptor ectodomain is elevated in the plasma of payientswith diabetesmellitus.2007

    • Author(s)
      Toshiyuki Obata
    • Journal Title

      Diabetes 56

      Pages: 2028-2035

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] APS-mediated Ubiquitination of the Insulin Receptor Enhances its Internalization, but does not Induce its Degradation.2007

    • Author(s)
      Kishi K.
    • Journal Title

      Endocrine Journal 54・(1)

      Pages: 77-88

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Angiotensin II inhibits insulin-induced actin stress fiber formation and glucose uptake via ERK1/22007

    • Author(s)
      Nazari H.
    • Journal Title

      The Journal of Medical Investigation 54・(1,2)

      Pages: 19-27

    • Related Report
      2006 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi