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MOLECULAR ANALYSIS OF STRUCTURE-FUNCTION RELATIONSHIP OF GLUCOSE TRANSPORTER AND INSULIN ACTION

Research Project

Project/Area Number 06454333
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionYAMAGUCHI UNIVERSITY

Principal Investigator

OKA Yoshitomo  YAMAGUCHI UNIVERSITY SCHOOL OF MEDICINE PROFESSOR, 医学部, 教授 (70175256)

Co-Investigator(Kenkyū-buntansha) ZAITU Yuzuru  YAMAGUCHI UNIVERSITY SCHOOL OF MEDICINE INSTRUCTOR, 医学部・附属病院, 医員
YOSHIDA Tuyoshi  YAMAGUCHI UNIVERSITY SCHOOL OF MEDICINE INSTRUCTOR, 医学部・附属病院, 医員
TANIZAWA Yukio  YAMAGUCHI UNIVERSITY SCHOOL OF MEDICINE ASSISTSNT PROFESSOR, 医学部・附属病院, 助手 (00217142)
谷沢 幸生  山口大学, 医学部附属病院, 医員
奥屋 茂  山口大学, 医学部, 助手 (20214083)
井上 康  山口大学, 医学部附属病院, 助手 (10176448)
松谷 朗  山口大学, 医学部附属病院, 講師 (10190464)
矢賀 健  山口大学, 医学部附属病院, 講師 (10166473)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1995: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1994: ¥4,400,000 (Direct Cost: ¥4,400,000)
Keywordsglucose transporter / glucose transport / molecular engineering / fructose transport / インスリン
Research Abstract

The biological and biochemical properties of glucose transpoter isoforms have been investigated. The rat GLUT5 cDNA was transfected into Chinese hamster ovary cells with an expression vector. GLUT5 was exclusively targeted to the plasma membrane and exhibited a transport activity, not for glucose, but for fructose with much higher affinity than GLUT2, the other glucose transporter with fructose transport activity. Interestingly, GLUT5 was not photolabeled with cytochalasin B,while a similar amount of GLUT1 was adequately photolabeled under the same experimental conditions. In addition, to elucidate the domains responsible for transport of glucose/fructose in GLUT1 and/or GLUT5, several chimeric GLUT1/GLUT5 proteins were expressed and their glucose transport and/or fructose transport activities were examined. The intracellular middle loop as well as the region encompassing from the 7th through the 12th membrane spanning domain were observed to have a crucial role in glucose transport of GLUT1, while replacement of the N-terminal half or the intracellular C-terminal region with the corresponding region of GLUT5 did not induce a marked effect on glucose transport activity. In contrast, both the N-terminal half from the N-terminus through the 6th membrane spanning domain and the intracellular C-terminal region were mandatory for fructose transport of GLUT5. Thus, GLUT5 is a transporter exclusively for fructose and the structure required for fructose transport is more stringent than that for glucose transport in hexose transporter proteins.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Ishihara H, et al.: "Inhibition of pancreatic β-cell glucokinase by antisense RNA expression in transgenic mice : mouse strain-dependent alteration of glucose tolerance." FEBS Letters. 371. 329-332 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tadokoro C, et al.: "Expresson and localization of glucose trandporter 1(GLUT1) in the rat oviduct ; a possible supplir of glucose to embryo during early embryonic development." Biochem Biophys Res Commun. 214. 1211-1218 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ishida K, et al.: "Regulation of glucose transporter I(GLUT1) gene expression by epidermal growth factor in bovine comeal endothelial cells." Japanese Journal Of Ophthalmology. 39. 225-232 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Inukai K, et al.: "Characterization of rat GLUT5 and functional analysis of chimeric proteins of GLUT1 glucose transorter and GLUT5 fructose transporter." Endocrinology. 136. 4850-4857 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ishihara H, et al.: "Human GLUT-2 overexpression does not affect glucose-stimulated insulin secretion in MIN6 cells." Am. J. Physiol.269. 897-902 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Katagiri H, et al.: "A novel isoform of syntaxin-binding protein homologous to yeast Secl expressed ubiquitously in mammalian cells." J Biol Chem. 270. 4963-4966 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ishihara H,et al.: "Overexpression of hexokinase I but not GLUT1 glucose transporter alters concentration-dependency of glucose-stimulated insulin secretion in pancreatic b-cell line MIN6." J.Biol Chem. 269. 3081-3087 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Inukai K,et al.: "Replacement of both tryptophan residues at 388 and 412 completely abolished cytochalasin B photolabelling of the GLUT1 glucose transporter." Biochem.J.302. 355-361 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Morita Y,et al.: "Glucose transporter GLUT1 mRNA expression in the ontogeny of glucose incorporation in mouse preimplantation embryos." Biochem Biophys Res Commun. 199. 1525-1531 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Morita Y,et al.: "Application of reverse transcription polymerase chain reaction to study the glucose transporter protein gene (GLUT) expression in preimplantation mouse embryo." J Mamm Ova Res. 11. 1-7 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Oka Y.: "NIDDM-genetic marker ; glucose tarasporter, glucokinase, and mitochondria gene." Diabetes Reserch and Clinical Practice. 24. 117-121 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tadokoro C,et al.: "Expresson and localization of glucose trandporter 1 (GLUT1) in the rat oviduct ; a possible supplir of glucose to embryo during early embryonic development." Biochem Biophys Res Commun. 214. 1211-1218 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Inukai K,et al.: "Characterization of rat GLUT5 and functional analysis of chimeric proteins of GLUT1 glucose transorter and GLUT5 fructose transporter." Endocrinology. 136. 4850-4857 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ishihara H,et al.: "Human GLUT-2 overexpression dose not affect glucose-stimulated insulin secretion in MIN6 cells." Am.J.Physiol. 269. 897-902 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ishida K.et al.: "Regulation of glucose transporter 1 (GLUT1) gene experssion by epidermal growth factor in bovine corneal endothelial cells." Japanese Journal Of Ophthalmology. 39. 225-232 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Katagiri H,et al.: "A novel isoform of syntaxin-binding protein homologous to yeast Secl expressed ubiquitously in mammalian cells." J Biol Chem. 270. 4963-4966 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ishihara H,et al.: "Inhibition of pancreatic β-cell glucokinase by antisense RNA expression in transgenic mice : mouse strain-dependent alteration of glucose tolerance." FEBS Letters. 371. 329-332 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tadokoro C,et al.: "Expresson and localization of glucose trandporter 1 (GLUT1) in the rat oviduct ; a possible supplir of glucose to embryo during early embryonic development." Biochem Biophys Res Commun. 214. 1211-1218 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ishida K,et al.: "Regulation of glucose transporter 1 (GLUT1) gene expression by epidermal growth factor in bovine corneal endothelial cells." Japanese Journal of Ophthalmology. 39. 225-232 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Inukai K,et al.: "Characterization of rat GLUT5 and functional analysis of chimeric proteins of GLUT1 glucose transorter and GLUT5 fructose transporter." Endocrinology. 136. 4850-4857 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ishihara H,et al.: "Human GLUT-2 overexpression does not affect glucose-stimulated insulin secretion in MIN6 cells." Am.J.Physiol.269. 897-902 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Katagiri H,et al.: "A novel isoform of syntaxin-binding protein homologous to yeast Secl expressed ubiquitously in mammalian cells." J Biol Chem. 270. 4963-4966 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Katagiri H.,et al: "A novel isotorm of syntaxin-binding protein homologous to yeast Secl expressed ubiquitously in mammalian cells." J Biol Chem. 270(印刷中). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ishihara H.,et al: "Overexpression of hexokinase I but not.GLUT1 glucose transporter alters concentration-dependency of glucose-stimulated insulin secretion in pancreatic b-cell line MIN6." J.Biol Chem. 269. 3081-3087 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Inukai K.,et al: "Replacement of both tryptophan residues at 388 and 412 completely abolished cytochalasin B photolabelling of GLUT1 glucose transporter." Biochem J.302. 355-361 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Morita Y.,et al: "Glucose transporter GLUT1 mRNA expression in the ontogeny of glucose incorporation in mouse preimplantation embryos." Biochem Biophys Res Commun. 199. 1525-1531 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Katagiri H.,et al: "Mitochondrial diabetes mellitus:prevalence and clinical characterization of diabetes due to mitochondrial tRNALeu(UUR) gene mutation in Japanese." Diabetologia. 37. 504-510 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Morita Y.,et al: "Application of reverse transcription-polymerase chain reaction to study the glucose transporter protein gene(GLUT) expression in preimplantation mouse embryo." J Mamm Ova Res. 11. 1-7 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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