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Study of Insulin resistance involving impaired GLUT4 translocation

Research Project

Project/Area Number 22590969
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionTohoku University

Principal Investigator

KANZAKI Makoto  東北大学, 大学院・医工学研究科, 准教授 (10272262)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsGLUT4 / 細胞内小胞輸送系 / 骨格筋 / 脂肪細胞 / 細胞内情報伝達系 / Vps10p / イメージング / 肥満 / 2型糖尿病 / 運動効果 / ソーティング / 細胞内小胞輸送 / 細胞内シグナル伝達 / インスリン抵抗性 / ソーティング障害 / ゴルジ体 / 筋細胞 / Sortlin / 2型糖尿病
Research Abstract

Defective insulin-responsive GLUT4 translocation is the earliest detectable feature of insulin resistance. Biochemical and nanometrological analyses herein revealed that sortilin, a member of the Vps10p-family sorting receptor, plays a critical role in establishing trans-Golgi network system specialized for generating the insulin-responsive GLUT4-strage vesicles that emerged to be severely deranged under certain insulin resistant conditions. This study thereby unmasks that insulin resistance is caused by not only defects in insulin signaling but also impairment of GLUT4 trafficking itself (“sorting disorder").

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (56 results)

All 2013 2012 2011 2010 Other

All Journal Article (26 results) (of which Peer Reviewed: 17 results) Presentation (25 results) Remarks (3 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Regulatory mode shift of Tbc1d1 is required for acquisition of insulin-responsive GLUT4 trafficking activity.2013

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

      Molecular Biology of the Cell

      Volume: 24 Issue: 6 Pages: 809-817

    • DOI

      10.1091/mbc.e12-10-0725

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of IL-6 production by electric pulse stimulation in contractile C2C12 myotubes.2013

    • Author(s)
      Farmawati A, Kitajima, Nedachi T, Sato M,Kanzaki M, Nagatomi R.
    • Journal Title

      Endocrine Journal

      Volume: 60(2) Pages: 137-147

    • URL

      http://dx.doi.org/10.1507/endocrj.EJ12-0316

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of contraction-induced IL-6 up-regulation using contractile C2C12 myotubes2013

    • Author(s)
      A. Farmawati, Y. Kitajima, T. Nedachi, M. Sato, M. Kanzaki, R. Nagatomi
    • Journal Title

      Endocrine Journal

      Volume: 60 Issue: 2 Pages: 137-147

    • DOI

      10.1507/endocrj.EJ12-0316

    • NAID

      10031156733

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] オルガネラ膜の直接パッチクランプ解析によるTPC1/2機能の解明2013

    • Author(s)
      神崎 展
    • Journal Title

      実験医学

      Volume: 31(1) Pages: 59-60

    • Related Report
      2012 Annual Research Report
  • [Journal Article] アストロサイト由来のglypicansと中枢神経ネットワークの構築2012

    • Author(s)
      神崎 展
    • Journal Title

      実験医学

      Volume: 30(16) Pages: 2600-2601

    • Related Report
      2012 Annual Research Report
  • [Journal Article] 細胞移動を支配するメカノセンシングのしくみ2012

    • Author(s)
      神崎 展
    • Journal Title

      実験医学

      Volume: 30(6) Pages: 936-937

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Molecular basis of insulin-responsive GLUT4 trafficking systems revealed by single molecule imaging2011

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

      Traffic

      Volume: 12 Issue: 12 Pages: 1805-1820

    • DOI

      10.1111/j.1600-0854.2011.01279.x

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Non-muscle myosin II induces disassembly of actin stress fibres independently of myosin light chain dephosphorylation2011

    • Author(s)
      Matsui, T.S., Kaunas, R., Kanzaki, M., Sato, M., Deguchi, S.
    • Journal Title

      Interface Focus

      Volume: 1 Issue: 5 Pages: 754-766

    • DOI

      10.1098/rsfs.2011.0031

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clustering of GLUT4, TUG and RUVBL2 protein levels correlate with myosin heavy chain isoform pattern in skeletal muscles, but AS160 and TBC1D1 levels do not2011

    • Author(s)
      C.M.Castorena
    • Journal Title

      Journal of Applied Physiology

      Volume: 111 Issue: 4 Pages: 1106-1117

    • DOI

      10.1152/japplphysiol.00631.2011

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spatiotemporally controlled contraction of micropatterned skeletal musclecells on a hydrogel sheet2011

    • Author(s)
      Nagamine K, Kawashima T, Sekine S, Ido Y,Takeda M, Otani S, Kumagai Y, Kanzaki, M, Nishizawa, M
    • Journal Title

      Lab on aChip

      Volume: 11(3) Issue: 3 Pages: 513-517

    • DOI

      10.1039/c0lc00364f

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sortilinとソーティング障害、そして生活習慣病2011

    • Author(s)
      神崎展
    • Journal Title

      生化学

      Volume: 83(11) Pages: 1035-1039

    • NAID

      10030345686

    • Related Report
      2011 Annual Research Report
  • [Journal Article] 生活習慣病とSorting Disorder2011

    • Author(s)
      神崎展
    • Journal Title

      実験医学

      Volume: 29(3) Pages: 430-431

    • Related Report
      2011 Annual Research Report
  • [Journal Article] 温度センサーとして機能するロドプシンとTRPA12011

    • Author(s)
      神崎展
    • Journal Title

      実験医学

      Volume: 29(9) Pages: 1564-1565

    • Related Report
      2011 Annual Research Report
  • [Journal Article] カベオリンによる力学的微細環境構築とガンの浸潤2011

    • Author(s)
      神崎展
    • Journal Title

      実験医学

      Volume: 29(16) Pages: 2655-2656

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Role of p120 catenin in the morphological changes of endothelial cells exposed to shear stress2010

    • Author(s)
      N. Sakamoto, K. Segawa, M. Kanzaki, T. Ohashi, M. Sato
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: Vol. 398 Issue: 3 Pages: 426-432

    • DOI

      10.1016/j.bbrc.2010.06.092

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Electrically inducedcontraction of C2C12 myotubes cultured on a porous membrane-based substrate with muscle tissue-like stiffness2010

    • Author(s)
      Kaji H., Ishibashi T., Nagamine K., Kanzaki,M., Nishizawa M.
    • Journal Title

      Biomaterials

      Volume: 31 Issue: 27 Pages: 6981-6986

    • DOI

      10.1016/j.biomaterials.2010.05.071

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Palmitate-induced Down-regulation of Sortilin and Impaired GLUT4 Trafficking inC2C12 myoutbues2010

    • Author(s)
      Tsuchiya Y., Hatakeyama H., Emoto N.,Wagatsuma F., Matsushita S., Kanzaki M.
    • Journal Title

      J.Biol.Chem

      Volume: 285(45) Issue: 45 Pages: 34371-34381

    • DOI

      10.1074/jbc.m110.128520

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification ofthree distinct functional sites ofinsulin-mediated GLUT4 Trafficking in Adipocytes using Quantitative Single Molecule Imaging2010

    • Author(s)
      Fujita H, Hatakeyama H, Watanabe TM, SatoM, Higuchi H, Kanzaki M.
    • Journal Title

      Mol Biol Cell

      Volume: 21(15) Issue: 15 Pages: 2721-2731

    • DOI

      10.1091/mbc.e10-01-0029

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Topographic Imaging of Convoluted Live Cells by Scanning IonConductance Microscopy in a Standing Approach Mode2010

    • Author(s)
      Takahashi Y, Murakami Y, Nagamine K,Shiku H, Aoyagi S, Yasukawa T, Kanzaki M, Matsue T.
    • Journal Title

      Phys Chem Chem Phys

      Volume: 12(34) Issue: 34 Pages: 10012-10017

    • DOI

      10.1039/c002607g

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cartee GD. In Vivo ExerciseFollowed by In Vitro Contraction AdditivelyElevates Subsequent Insulin-stimulatedGlucose Transport by Rat Skeletal Muscle2010

    • Author(s)
      Funai, K, Schweitzer GG, Castorena CM,Kanzaki, M
    • Journal Title

      Am J Physiol Endocrinol Metab

      Volume: 298(5) Issue: 5 Pages: E999-E1010

    • DOI

      10.1152/ajpendo.00758.2009

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Micropatterning Contractile C2C12 Myotubes Embedded in a Fibrin Gel2010

    • Author(s)
      Nagamine K, Kawashima T, Ishibashi T., KajiH, Kanzaki M, Nishizawa M.
    • Journal Title

      Biotechnology and Bioengineering

      Volume: 105(6) Issue: 6 Pages: 1161-1167

    • DOI

      10.1002/bit.22636

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Palmitate-induced Down-regulation of Sortilin and Impaired GLUT4 Trafficking in C2C12 myoutbues.2010

    • Author(s)
      Tsuchiya Y.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 285 Pages: 34371-34381

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of three distinct functional sites of insulin-mediated GLUT4 Trafficking in Adipocytes using Quantitative Single Molecule Imaging2010

    • Author(s)
      Fujita H.
    • Journal Title

      Molecular Bioiogy of the Cell

      Volume: 21 Pages: 2721-2731

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In Vivo Exercise Followed by In Vitro Contraction Additively Elevates Subsequent Insulin-stimulated Glucose Transport by Rat Skeletal Muscle2010

    • Author(s)
      Funai K.
    • Journal Title

      American Journal of Physiology, Endocrinology & Metabolism

      Volume: 298

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular Basis of Static GLUT4 Storage Compartment Formation in 3T3-L1 Adipocytes Revealed by Quantum Dot-Based Quantitative Single Molecular Imaging2010

    • Author(s)
      Hatakeyama H
    • Journal Title

      Diabetes

      Volume: 59(Supple)

    • Related Report
      2010 Annual Research Report
  • [Journal Article] 収縮活動可能な培養筋管細胞系の構築とその代謝研究への応用2010

    • Author(s)
      神崎展
    • Journal Title

      内分泌・糖尿病・代謝内科

      Volume: 31 Pages: 464-471

    • Related Report
      2010 Annual Research Report
  • [Presentation] Identification of Novel"Exercise Factors" using ContractileMyotube Model2012

    • Author(s)
      Kanzaki, M.
    • Organizer
      International Symposium on Cellular Mechanobiology
    • Place of Presentation
      Kyoto University Clock Tower Centennial Hall,Kyoto
    • Year and Date
      2012-03-16
    • Related Report
      2012 Final Research Report
  • [Presentation] Identification of Novel "Exercise Factors" using Contractile Myotube Model2012

    • Author(s)
      Makoto Kanzaki
    • Organizer
      International Symposium on Cellular Mechanobiology
    • Place of Presentation
      Kyoto University, Clock Tower Centennial Hall (Kyoto)
    • Year and Date
      2012-03-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Impact of Akt1 and 2 on TBC1D1/D4 in response to glucose in beta-cells2012

    • Author(s)
      Rutti, S., Kaddai, V., Negro, V., Kanzaki,M., Halban, PA., Bouzakri, K.
    • Organizer
      48^<th> Annual Meeting of the European Association for the Studyof Diabetes. EASD meeting
    • Place of Presentation
      Berlin, Germany
    • Related Report
      2012 Final Research Report
  • [Presentation] Characterization of Unique RegulatoryMechanism of Tbc1d1 in GLUT4 Trafficking by Single Molecule Analysis of GLUT4 Behavior2012

    • Author(s)
      Hatakeyama, H and Kanzaki, M.
    • Organizer
      72^<nd> American Diabetes Association Scientific Meeting
    • Place of Presentation
      Pennsylvania Convention Center,Philadelphia, PA, USA
    • Related Report
      2012 Final Research Report
  • [Presentation] Characterization of Unique Regulatory Mechanism of Tbc1d1 in GLUT4 Trafficking by Single Molecule Analysis of GLUT4 Behavior.2012

    • Author(s)
      Hatakeyama H.
    • Organizer
      American Diabetes Association Scientific Meeting,
    • Place of Presentation
      Philadelphia, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Unique Regulatory Mechanism of Tbc1d1 RabGAP in GLUT4 Trafficking Revealed by Single Molecule Imaging of GLUT4 Behavior.2012

    • Author(s)
      Hatakeyama H
    • Organizer
      American Society for Cell Biology Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Impact of Akt1 and 2 on TBC1D1/D4 in response to glucose in beta-cells.2012

    • Author(s)
      Rutti, S
    • Organizer
      48th Annual Meeting of the European Association for the Study of Diabetes.
    • Place of Presentation
      Berlin, Germany
    • Related Report
      2012 Annual Research Report
  • [Presentation] GLUT4輸送調節におけるAS160とTbc1d1の作用点とその分子機序2012

    • Author(s)
      畠山裕康
    • Organizer
      第55回日本糖尿病学会
    • Place of Presentation
      横浜 パシフィコ横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] Distinct Roles of Two Rab GAPs, AS160/Tbc1d4 and Tbc1d1, on Intracellular GLUT4 Trafficking Analyzed with Single Molecule Imaging of GLUT4 Behavior2011

    • Author(s)
      Hatakeyama H.
    • Organizer
      51^<st> American Society for Cell Biology Annual Meeting
    • Place of Presentation
      Colorado Convention Center (CO, USA)
    • Year and Date
      2011-12-05
    • Related Report
      2011 Annual Research Report
  • [Presentation] 細胞内輸送の新規定量的解析系を用いたインスリン応答性GLUT4輸送システムの分子基盤解析2011

    • Author(s)
      畠山裕康
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2011-09-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] Critical roles of sortilin in GLUT4 trafficking systems and insulin resistant state revealed by single molecule imaging of GLUT4 behavior2011

    • Author(s)
      Hatakeyama H.
    • Organizer
      FASEB Summer Research Conference "Glucose Transporters, Signaling and Diabetes"
    • Place of Presentation
      Snowmass Village Conference Center (CO, USA)
    • Year and Date
      2011-08-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Impaired Biogenesis of the Insulin-responsive GLUT4 Storage Compartment under Insulin Resistance Revealed by Single Molecule Imaging2011

    • Author(s)
      Hatakeyama H.
    • Organizer
      71^<st> American Diabetes Association Scientific Sessions
    • Place of Presentation
      San Diego Convention Center (CA, USA)
    • Year and Date
      2011-06-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] GLUT4のソーティング障害と2型糖尿病2011

    • Author(s)
      神崎展
    • Organizer
      第6回トランスポーター研究会
    • Place of Presentation
      東北大学さくらホール(仙台)(招待講演)
    • Year and Date
      2011-06-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] 一分子動態計測系に基づくインスリン応答性GLUT4輸送システムの分子基盤解析2011

    • Author(s)
      畠山裕康
    • Organizer
      第54回日本糖尿病学会学術集会
    • Place of Presentation
      札幌芸術文化の館(札幌)
    • Year and Date
      2011-05-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] Distinct Roles of Two Rab GAPs, AS160/Tbc1d4and Tbc1d1, on Intracellular GLUT4Trafficking Analyzed with Single Molecule Imaging of GLUT4 Behavior2011

    • Author(s)
      Hatakeyama, H and Kanzaki, M.
    • Organizer
      51^<st> American Society for Cell Biology Annual Meeting
    • Place of Presentation
      Denver, CO. USA
    • Related Report
      2012 Final Research Report
  • [Presentation] Criticalroles of sortilin in GLUT4 trafficking systems and insulin resistant state revealedby single molecule imaging of GLUT4 behavior2011

    • Author(s)
      Hatakeyama, H and Kanzaki, M.
    • Organizer
      FASEB Summer Research Conference "Glucose Transporters,Signaling and Diabetes"
    • Place of Presentation
      Snowmass Village, CO. USA
    • Related Report
      2012 Final Research Report
  • [Presentation] Impaired Biogenesis of theInsulin-responsive GLUT4 Storage Compartment under Insulin Resistance Revealed by Single Molecule Imaging2011

    • Author(s)
      Hatakeyama, H and Kanzaki, M.
    • Organizer
      71^<st> American Diabetes Association ScientificSessions 2011
    • Place of Presentation
      San Diego, CA. USA
    • Related Report
      2012 Final Research Report
  • [Presentation] GLUT4のソーティング障害と2型糖尿病2011

    • Author(s)
      神崎展
    • Organizer
      第6回トランスポーター研究会
    • Place of Presentation
      仙台
    • Related Report
      2012 Final Research Report
  • [Presentation] Roles of Sortilim-Mediated Retrograde Trafficking in Insulin-Responsive GLUT4 Trafficking Systems Analyzed with Single Molecule Imaging of GLUT4 Behavior2010

    • Author(s)
      Hatakeyama H
    • Organizer
      50^<th> American Society for Cell Biology Meeting
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2010-12-06
    • Related Report
      2010 Annual Research Report
  • [Presentation] 運動刺激によって活性化される細胞内シグナル伝達系とマイオカイン分泌制御2010

    • Author(s)
      神崎展
    • Organizer
      第22回運動器リハビリテーション学会・シンポジウム
    • Place of Presentation
      仙台
    • Year and Date
      2010-07-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] Molecular Basis of Static GLUT4 Storage Compartment Formation in 3T3-L1 Adipocytes Revealed by Quantum Dot-Based Quantitative Single Molecular Imaging2010

    • Author(s)
      Hatakeyama H
    • Organizer
      70^<th> American Diabetes Association, Scientific Meeting
    • Place of Presentation
      Orlando, FL, USA
    • Year and Date
      2010-06-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] Palmitate-induced Down-regulation of Sortilin and Insulin Resistance in Skeletal Muscle Cells.2010

    • Author(s)
      Kanzaki M
    • Organizer
      International Congress "Sortilins in Sorting and Disease"
    • Place of Presentation
      Aarhus, DENMARK
    • Year and Date
      2010-06-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] ナノ蛍光粒子を用いたインスリン反応性GLUT4分子挙動変化の解析2010

    • Author(s)
      神崎展
    • Organizer
      第53回日本糖尿病学会年次学術集会・シンポジウム
    • Place of Presentation
      岡山
    • Year and Date
      2010-05-30
    • Related Report
      2010 Annual Research Report
  • [Presentation] GLUT4一分子動態追跡系を用いたGLUT4 storage compartment形成機構の定量解析2010

    • Author(s)
      畠山裕康
    • Organizer
      第53回日本糖尿病学会年次学術集会
    • Place of Presentation
      岡山
    • Year and Date
      2010-05-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] Quantum Dot(Qdot)を用いたGLUT4細胞内小胞輸送系の定量的解析2010

    • Author(s)
      神崎 展
    • Organizer
      第8回日本ナノ学会・シンポジウム
    • Place of Presentation
      岡崎
    • Year and Date
      2010-05-14
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      https://www.researchgate.net/profile/Makoto_Kanzaki/

    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://www.ecei.tohoku.ac.jp/kanzaki/index.html

    • Related Report
      2012 Final Research Report
  • [Remarks] ResearchGate

    • URL

      https://www.researchgate.net/profile/Makoto_Kanzaki/

    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] Cultured Muscle Cells with High Metabolic Activity and Methods for Production of the Cultured Muscle Cells2011

    • Inventor(s)
      Kanzaki, M., Nedachi,T., Fujita, H.
    • Industrial Property Rights Holder
      東北大学
    • Filing Date
      2011-11-09
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] インスリン反応性糖輸送担体の膜移行活性が測定可能な培養筋細胞2011

    • Inventor(s)
      神崎展・根建拓
    • Industrial Property Rights Holder
      東北大学
    • Filing Date
      2011-07-01
    • Related Report
      2012 Final Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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