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Molecular and structural basis of insulin resistance revealed by high precision nanometry

Research Project

Project/Area Number 25713010
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field General physiology
Research InstitutionTohoku University

Principal Investigator

Hatakeyama Hiroyasu  東北大学, 学際科学フロンティア研究所, 助教 (00619067)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥24,570,000 (Direct Cost: ¥18,900,000、Indirect Cost: ¥5,670,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥20,930,000 (Direct Cost: ¥16,100,000、Indirect Cost: ¥4,830,000)
Keywords糖輸送体 / ライブイメージング
Outline of Final Research Achievements

The aim of this study was to understand the molecular and structural basis of insulin resistance, a characteristic etiology of type 2 diabetes, by improving the GLUT4 nanometry and performing high-precision measurements of GLUT4 trafficking regulatory systems. To achieve this, we first established a new experimental and analytical system for performing GLUT4 nanometry, with which we successfully performed simultaneous high-precision imaging of single molecule behavior of two distinct trafficking molecules and observed single molecule behavior and subcellular structures simultaneously. Furthermore, we enabled GLUT4 nanometry in isolated mice skeletal myofibers, which have higher-order structures and functions than cell line cultures, used in previous studies do. Using skeletal myofibers, combined with a cell-based reconstitution model, we revealed GLUT4 trafficking systems and the molecular basis of exercise effects on skeletal muscles.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (18 results)

All 2016 2015 2014 2013 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (16 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Journal Article] Single quantum dot tracking reveals that an individual multivalent 2 HIV-1 Tat-protein transduction domain can activate machinery for 3 lateral transport and endocytosis2013

    • Author(s)
      3.Yasuhiro Suzuki*, Chandra Nath Roy, Warunya Promjunyaku, Hiroyasu Hatakeyama, Kohsuke Gonda, Junji Imamura, Biju Vasudevan Pillai, Noriaki Ohuchi, Makoto Kanzaki , Hideo Higuchi, and Mitsuo Kaku
    • Journal Title

      Mol. Cell Biol.

      Volume: 33 Issue: 15 Pages: 3039-3049

    • DOI

      10.1128/mcb.01717-12

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of dual-color simultaneous single molecule imaging system for analyzing multiple intracellular trafficking activities2013

    • Author(s)
      Hatakeyama H, Kanzaki M.
    • Journal Title

      Conf Proc IEEE Eng Med Biol Soc.

      Volume: 2013 Pages: 1418-1421

    • DOI

      10.1109/embc.2013.6609776

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] マウス走行運動モデルと電気パルス強収縮モデルを用いた収縮骨格筋の生物学的応答の解析―GLUT4制御に関わる分子基盤について―2016

    • Author(s)
      細谷 雅浩、堰合 茂智、畠山 裕康、神崎 展
    • Organizer
      第4回骨格筋生物学研究会
    • Place of Presentation
      松本
    • Year and Date
      2016-03-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] AS160 vs Tbc1d1: Cooperative determination of insulin-responsive GLUT4 trafficking activity after exercise-mimetic stimuli2015

    • Author(s)
      Hiroyasu Hatakeyama, Makoto Kanzaki
    • Organizer
      51st Annual Meeting of the European Association for the Study of Diabetes
    • Place of Presentation
      ストックホルム(スウェーデン)
    • Year and Date
      2015-09-14
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 一分子計測で迫る糖輸送体分子の細胞内輸送システム2015

    • Author(s)
      畠山 裕康
    • Organizer
      東海大学マイクロ・ナノ研究開発センター第14回講演会、バイオイメージングセミナー
    • Place of Presentation
      平塚
    • Year and Date
      2015-08-03
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Coordinated actions of AS160 and Tbc1d1 as a determinant of insulin sensitivity in GLUT4 trafficking2015

    • Author(s)
      Hiroyasu Hatakeyama, Makoto Kanzaki
    • Organizer
      FASEB SRC "Glucose Transport: Gateway to Metabolic Systems Biology"
    • Place of Presentation
      ビッグスカイ(アメリカ・モンタナ州)
    • Year and Date
      2015-07-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Involvement of Mechanosensitive Transcriptional Network in Contraction-dependent Muscle Fiber Type Conversion Analyzed using the "in vitro Exercise Model"2015

    • Author(s)
      Masahiro Hosoya, Yuhei Uda, Hiroyasu Hatakeyama, Makoto Kanzaki
    • Organizer
      Cell Symposia "Exercise Metabolism"
    • Place of Presentation
      アムステルダム(オランダ)
    • Year and Date
      2015-07-12
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] GLUT4一分子挙動計測に基づくTBC/RabGAPsが司る運動効果の分子基盤解析2015

    • Author(s)
      畠山 裕康、神崎 展
    • Organizer
      第3回骨格筋生物学研究会
    • Place of Presentation
      仙台
    • Year and Date
      2015-03-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] Submissive Role of AS160 in Tbc1d1-mediated GLUT4 Trafficking Activation in response to Ca2+ and Insulin2014

    • Author(s)
      Hiroyasu Hatakeyama, Makoto Kanzaki
    • Organizer
      74th Science Sessions of the American Diabetes Association
    • Place of Presentation
      San Francisco, CA, USA
    • Year and Date
      2014-06-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] 一分子イメージングに基づく細胞内輸送システムの定量計測2014

    • Author(s)
      畠山 裕康、神崎 展
    • Organizer
      バイオイメージインフォマティクス2014
    • Place of Presentation
      岡崎
    • Year and Date
      2014-06-09 – 2014-06-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] インスリン応答性GLUT4輸送制御におけるTBC1D family Rab GTPase活性化タンパク質群の機能解析2014

    • Author(s)
      畠山 裕康、神崎 展
    • Organizer
      第57回日本糖尿病学会年時学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] Intracellular trafficking nanometry for quantifying GLUT4 translocation2013

    • Author(s)
      Hatakeyama H, Kanzaki M
    • Organizer
      FASEB Science Research Conference "Glucose transport: Gateway for metabolic systems biology"
    • Place of Presentation
      Snowmass Village, CO, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Tbc1d1が示すインスリン不応性およびインスリン応答性GLUT4輸送制御とその遷移による「インスリン応答性獲得」の分子基盤

    • Author(s)
      畠山 裕康、神崎 展
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] Molecular basis of Tbc1d1 for acquiring temporal insulin-responsive ability triggering GLUT4 translocation

    • Author(s)
      Hatakeyama H, Kanzaki M
    • Organizer
      American Diabetes Association's 73rd Scientific Session
    • Place of Presentation
      Chicago, IL, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Development of dual-color simultaneous single molecule imaging system for analyzing multiple intracellular trafficking activities.

    • Author(s)
      Hatakeyama H, Kanzaki M
    • Organizer
      35th Annual International Conference of IEEE Eng Med Biol Soc
    • Place of Presentation
      Osaka, Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] 分子動態に基づく細胞内輸送システムの定量解析

    • Author(s)
      畠山 裕康
    • Organizer
      北海道大学電子科学研究所 第2回蛍光ミニシンポジウム
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Comprehensive viewing of intracellular trafficking activities based on single molecule imaging

    • Author(s)
      Hatakeyama H, Kanzaki M
    • Organizer
      American Society for Cell Biology 2013 Annual Meeting
    • Place of Presentation
      New Orleans, LA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Establishment of intracellular trafficking nanometry in single isolated myofibers.

    • Author(s)
      Kaita S, Shinagawa R, Hatakeyama H, Kanzaki M
    • Organizer
      American Society for Cell Biology 2013 Annual Meeting
    • Place of Presentation
      New Orleans, LA, USA
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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