Study of Insulin resistance involving impaired GLUT4 translocation

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590969
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Tohoku 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
• Keywords: GLUT4 / 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

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").

Research Products

• [Journal Article] Regulatory Mode Shift of Tbc1d1 is Requiredfor insulin-responsive GLUT4 TraffickingActivity (2013)
  • Author(s): Hatakeyama H, and Kanzaki M.
  • Journal Title: Mol. Biol. Cell Volume: 24(6) Pages: 809-817
  • DOI: DOI:10.1091/mbc.E12-10-0725.
  • 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
  • Peer Reviewed
• [Journal Article] Molecular basis of insulin-responsive GLUT4 trafficking systems revealed by single molecule imaging (2011)
  • Author(s): Hatakeyama H, and Kanzaki,M
  • Journal Title: Traffic Volume: 12(12) Pages: 1805-1820
  • DOI: DOI:10.1111/j.1600-0854.2011.01279.x.
  • Peer Reviewed
• [Journal Article] Nonmuscle myosin II induces disassembly of actin stress fibers independently of myosin light chaindephosphorylation (2011)
  • Author(s): Matsui TS, Kaunas R, Kanzaki M.,Sato M.,Deguchi S.
  • Journal Title: Interface Focus Volume: 1(5) Pages: 754-766
  • DOI: DOI:10.1098/rsfs.2011.0031.
  • Peer Reviewed
• [Journal Article] Cartee, DG. Clustering ofGLUT4, TUG and RUVBL2 Protein LevelsCorrelate with Myosin Heavy Chain IsoformPattern in Skeletal Muscles, but AS160 andTBC1D1 Levels Do Not (2011)
  • Author(s): Castorena, CM., MacKrell, JG., Bogan, JS.,Kanzaki, M.
  • Journal Title: J. Appl. Physiol Volume: 111(4) Pages: 1106-1117
  • DOI: DOI:10.1152/japplphysiol.00631.2011.
  • Peer Reviewed
• [Journal Article] Spatiotemporally controlled contraction of micropatterned skeletal musclecells on a hydrogel sheet (2011)
  • 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) Pages: 513-517
  • DOI: DOI:10.1039/c0lc00364f.
  • Peer Reviewed
• [Journal Article] Role of p120-Catenin in Morphological Changes in Endothelial Cells Exposed to Fluid Shear Stress (2010)
  • Author(s): Sakamoto N., Segawa K., Kanzaki M., Ohashi T., Sato M
  • Journal Title: Biochem Biophys Res Commun Volume: 398(3) Pages: 426-432
  • DOI: DOI:10.1016/j.bbrc.2010.06.092.
  • Peer Reviewed
• [Journal Article] Electrically inducedcontraction of C2C12 myotubes cultured on a porous membrane-based substrate with muscle tissue-like stiffness (2010)
  • Author(s): Kaji H., Ishibashi T., Nagamine K., Kanzaki,M., Nishizawa M.
  • Journal Title: Biomaterials Volume: 31 Pages: 6981-6986
  • DOI: DOI:10.1016/j.biomaterials.2010.05.071.
  • Peer Reviewed
• [Journal Article] Palmitate-induced Down-regulation of Sortilin and Impaired GLUT4 Trafficking inC2C12 myoutbues (2010)
  • Author(s): Tsuchiya Y., Hatakeyama H., Emoto N.,Wagatsuma F., Matsushita S., Kanzaki M.
  • Journal Title: J.Biol.Chem Volume: 285(45) Pages: 34371-34381
  • DOI: DOI:10.1074/jbc.M110.128520.
  • Peer Reviewed
• [Journal Article] Identification ofthree distinct functional sites ofinsulin-mediated GLUT4 Trafficking in Adipocytes using Quantitative Single Molecule Imaging (2010)
  • Author(s): Fujita H, Hatakeyama H, Watanabe TM, SatoM, Higuchi H, Kanzaki M.
  • Journal Title: Mol Biol Cell Volume: 21(15) Pages: 2721-2731
  • DOI: DOI:10.1091/mbc.E10-01-0029.
  • Peer Reviewed
• [Journal Article] Topographic Imaging of Convoluted Live Cells by Scanning IonConductance Microscopy in a Standing Approach Mode (2010)
  • 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) Pages: 10012-10017
  • DOI: DOI:10.1039/c002607g.
  • Peer Reviewed
• [Journal Article] Cartee GD. In Vivo ExerciseFollowed by In Vitro Contraction AdditivelyElevates Subsequent Insulin-stimulatedGlucose Transport by Rat Skeletal Muscle (2010)
  • Author(s): Funai, K, Schweitzer GG, Castorena CM,Kanzaki, M
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 298(5) Pages: E999-1010
  • DOI: DOI:10.1152/ajpendo.00758.2009.
  • Peer Reviewed
• [Journal Article] Micropatterning Contractile C2C12 Myotubes Embedded in a Fibrin Gel (2010)
  • Author(s): Nagamine K, Kawashima T, Ishibashi T., KajiH, Kanzaki M, Nishizawa M.
  • Journal Title: Biotechnology and Bioengineering Volume: 105(6) Pages: 1161-1167
  • DOI: DOI:10.1002/bit.22636.
  • Peer Reviewed
• [Presentation] Impact of Akt1 and 2 on TBC1D1/D4 in response to glucose in beta-cells (2012)
  • 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
  • Year and Date: 20121001-05
• [Presentation] Characterization of Unique RegulatoryMechanism of Tbc1d1 in GLUT4 Trafficking by Single Molecule Analysis of GLUT4 Behavior (2012)
  • Author(s): Hatakeyama, H and Kanzaki, M.
  • Organizer: 72^<nd> American Diabetes Association Scientific Meeting
  • Place of Presentation: Pennsylvania Convention Center,Philadelphia, PA, USA
  • Year and Date: 20120608-12
• [Presentation] Identification of Novel"Exercise Factors" using ContractileMyotube Model (2012)
  • 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
• [Presentation] Distinct Roles of Two Rab GAPs, AS160/Tbc1d4and Tbc1d1, on Intracellular GLUT4Trafficking Analyzed with Single Molecule Imaging of GLUT4 Behavior (2011)
  • Author(s): Hatakeyama, H and Kanzaki, M.
  • Organizer: 51^<st> American Society for Cell Biology Annual Meeting
  • Place of Presentation: Denver, CO. USA
  • Year and Date: 20111203-07
• [Presentation] Criticalroles of sortilin in GLUT4 trafficking systems and insulin resistant state revealedby single molecule imaging of GLUT4 behavior (2011)
  • Author(s): Hatakeyama, H and Kanzaki, M.
  • Organizer: FASEB Summer Research Conference "Glucose Transporters,Signaling and Diabetes"
  • Place of Presentation: Snowmass Village, CO. USA
  • Year and Date: 20110814-19
• [Presentation] Impaired Biogenesis of theInsulin-responsive GLUT4 Storage Compartment under Insulin Resistance Revealed by Single Molecule Imaging (2011)
  • Author(s): Hatakeyama, H and Kanzaki, M.
  • Organizer: 71^<st> American Diabetes Association ScientificSessions 2011
  • Place of Presentation: San Diego, CA. USA
  • Year and Date: 20110624-28
• [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
  • Year and Date: 20110611-12
• [Remarks]
  • URL: https://www.researchgate.net/profile/Makoto_Kanzaki/
• [Remarks]
  • URL: http://www.ecei.tohoku.ac.jp/kanzaki/index.html
• [Patent(Industrial Property Rights)] Cultured Muscle Cells with High Metabolic Activity and Methods for Production of the Cultured Muscle Cells (2011)
  • Inventor(s): Kanzaki, M., Nedachi,T., Fujita, H.
  • Industrial Property Rights Holder: 東北大学
  • Industrial Property Number: 特許、特願US7,829,334 B2
  • Filing Date: 2011-11-09
• [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
  • Industrial Property Number: 特許、特願第4769935
  • Filing Date: 2011-07-01