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2013 Fiscal Year Final Research Report

Mechanism of insulin-induced GLUT4 down-regulation through retromer inhibition

Research Project

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Project/Area Number 23591295
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionGunma University

Principal Investigator

SHIBATA Hiroshi  群馬大学, 生体調節研究所, 准教授 (20235584)

Project Period (FY) 2011 – 2013
Keywordsインスリン / 活性酸素 / レトロマー / 脂肪細胞 / NADPHオキシダーゼ / GLUT4
Research Abstract

Long term insulin stimulation causes GLUT4 depletion. This effect is caused mainly by accelerated lysosomal degradation of GLUT4. We show that insulin acutely dissociated retromer from the LDM membranes of 3T3-L1 adipocytes that was accompanied by disruption of the interaction of Vps35 with sortilin. This insulin effect was dependent on protein kinase CK2 but not PI3-kinase or Erk 1/2. Knockdown of Vps26 decreased GLUT4 to a level comparable with that with insulin stimulation for 4 h. Vps35 with a mutation in the CK2 phosphorylation motif was resistant to insulin-induced dissociation from the low density microsomal membrane, and its overexpression attenuated GLUT4 down-regulation with insulin. Insulin-generated hydrogen peroxide was an upstream mediator of the insulin action on retromer and GLUT4. These results suggested that insulin-generated oxidative stress switches the GLUT4 sorting direction to lysosomes through inhibition of the retromer function in a CK2-dependent manner.

  • Research Products

    (12 results)

All 2014 2013 2012 2011 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (7 results) Remarks (1 results)

  • [Journal Article] Prolonged insulin stimulation down-regulates GLUT4 through oxidative stress-mediated retromer inhibition by a protein kinase CK2-dependent mechanism in 3T3-L1 adipocytes2014

    • Author(s)
      Ma J, Nakagawa Y, Kojima I, Shibata H
    • Journal Title

      J Biol Chem

      Volume: Vol.289 Pages: 133-142

    • DOI

      10.1074/jbc.M113.533240

    • Peer Reviewed
  • [Journal Article] Glucose promotes its own metabolism by acting on the cell-surface glucose-sensing receptor T1R32014

    • Author(s)
      Nakagawa Y, Ohtsu Y, Nagasawa M, Shibata H, Kojima I
    • Journal Title

      Endocr J

      Volume: Vol.61 Pages: 119-131

    • URL

      https://www.jstage.jst.go.jp/article/endocrj/61/2/61_EJ13-0431/_article

    • Peer Reviewed
  • [Journal Article] A novel regulatory function of sweet taste-sensing receptor in adipogenic differentiation of 3T3-L1 cells2013

    • Author(s)
      Masubuchi Y, Nakagawa Y, Ma J, Sasaki T, Kitamura T, Yamamoto Y, Kurose H, Kojima I, Shibata H
    • Journal Title

      PLoS ONE

      Volume: Vol.8 Pages: e54500

    • DOI

      10.1371/journal.pone.0054500

    • Peer Reviewed
  • [Journal Article] Miglitol prevents diet-induced obesity by stimulating brown adipose tissue and energy expenditure independent of preventing the digestion of carbohydrates2013

    • Author(s)
      Sasaki T, Shimpuku M, Kitazumi T, Hiraga H, Nakagawa Y, Shibata H, Okamatsu-Ogura Y, Kikuchi O, Kim HJ, Fujita Y, Maruyama J, Susanti VY, Yokota-Hashimoto H, Kobayashi M, Saito M, Kitamura T
    • Journal Title

      Endocr J

      Volume: Vol.60 Pages: 1117-1129

    • URL

      https://www.jstage.jst.go.jp/article/endocrj/60/10/60_EJ13-0333/_article

    • Peer Reviewed
  • [Presentation] Sweet taste receptor regulates adipogenesis through Gs-mediated microtubule disassembly and Rho activation in 3T3-L1 cells2013

    • Author(s)
      Masubuchi Y, Nakagawa Y, Ma J, Nagasawa M, Kojima I, Shibata H
    • Organizer
      73rd Scientific Session of American Diabetes Association
    • Place of Presentation
      マコーミックプレイス・コンベンションセンター(米国シカゴ市)
    • Year and Date
      20130621-25
  • [Presentation] 甘味刺激によるGs活性化は微小管脱重合とRho活性化を介して脂肪分化を抑制する2013

    • Author(s)
      増渕洋祐,中川祐子,馬金輝,長澤雅裕,小島至,柴田宏
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本市
    • Year and Date
      20130516-18
  • [Presentation] A novel regulatory function of sweet taste-sensing receptor in adipogenic differentiation of 3T3-L1 cells2012

    • Author(s)
      Masubuchi Y, Nakagawa Y, Ma J, Kojima I, Shibata H
    • Organizer
      72nd Scientific Session of American Diabetes Association
    • Place of Presentation
      ペンシルベニア・コンベンションセンター(米国フィラデルフィア市)
    • Year and Date
      20120608-12
  • [Presentation] 新規インスリン・シグナル分子PC-PLCによるNox4活性化機構2012

    • Author(s)
      馬金輝,小島至,柴田宏
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      20120517-19
  • [Presentation] 甘味受容体による脂肪細胞分化抑制のシグナル機構2012

    • Author(s)
      増渕洋祐,中川祐子,馬金輝,小島至,柴田宏
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      20120517-19
  • [Presentation] ホスファチジルコリン特異的PLCは脂肪細胞における活性酸素産生とGLUT4分解のインスリン・シグナルとして機能する2011

    • Author(s)
      馬金輝,小島至,柴田宏
    • Organizer
      第54回日本糖尿病学会年次学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      20110519-21
  • [Presentation] 脂肪細胞における甘味受容体の発現と機能2011

    • Author(s)
      増渕洋祐,中川祐子,馬金輝,小島至,柴田宏
    • Organizer
      第54回日本糖尿病学会年次学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      20110519-21
  • [Remarks]

    • URL

      http://www.imcr.gunma-u.ac.jp/lab/celphy/

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Published: 2015-07-16  

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