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Molecular manipulations to probe the relationship between structure and function of the glucose transporter

Research Project

Project/Area Number 04454557
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionUniversity of Tokyo

Principal Investigator

OKA Yoshitomo  THIRD DEPARTMENT OF INTERNAL MEDICINE FACULTY OF MEDICINE, UNIVERSITY OF TOKYO ASSISTANT PROFESSOR, 医学部・附属病院, 助手 (70175256)

Co-Investigator(Kenkyū-buntansha) INUKAI Kouichi  THIRD DEPARTMENT OF INTERNAL MEDICINE FACULTY OF MEDICINE, UNIVERSITY OF TOKYO R, 医学部・附属病院, 医員
ISHIHARA Hisamitu  THIRD DEPARTMENT OF INTERNAL MEDICINE FACULTY OF MEDICINE, UNIVERSITY OF TOKYO R, 医学部・附属病院, 医員
KATAGIRI Hideki  THIRD DEPARTMENT OF INTERNAL MEDICINE FACULTY OF MEDICINE, UNIVERSITY OF TOKYO R, 医学部・附属病院, 医員
ASANO Tomoichiro  THIRD DEPARTMENT OF INTERNAL MEDICINE FACULTY OF MEDICINE, UNIVERSITY OF TOKYO R, 医学部・附属病院, 助手 (70242063)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1993: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥3,700,000 (Direct Cost: ¥3,700,000)
Keywordsglucose transporter / structure and function / chimera / 遺伝子工学
Research Abstract

Recent cDNA cloning has disclosed the presence of a structurally related family of proteins that catalize facilitated glucose transporter across the plasma membranes. However, in spite of the marked similarity in structure, the tissue distribution and subcellular distribution, as well as characteristics of glucose transport, are different among isoforms. We have focused on a C-terminal domain, since it is diverse in size and amino acid sequence among glucose transporter isoforms. GLUT2 has far higher Km and Vmax values compared with GLUT1. To investigate the role pf the intracellular C-terminal domain in glucose transport, we expressed in Chinese hamster ovary cells the mutated GLUT1 whose intracellular C-terminal domain was replaced with that of GLUT2 by means of engineering the chimeric cDNA.Cytochalasin B, for which GLUT2 protein has much lower affinity, bound to this chimeric protein in a fashion similar to GLUT1. In contrast, greater transport activity was observed in this chimeric glucose transporter compared with the wild-type GLUT1 at 10 mM 2-deoxy-D-glucose concentration. The kinetic studies on 2-deoxy-D-glucose uptake revealed a 3.8-fold increase in Km and a 4.3-fold increase in Vmax in this chimeric glucose transporter compared with the wild-type GLUT1. Thus, replacement of the intracellular C-terminal domain confers the GLUT2-like property on the glucose transporter. These results strongly suggest that the diversity of intracellular C-terminal domain contributes to the diversity of glucose transport characteristics among isoforms.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Ishihara H et al.: "Expression of GLUT4 glucose transporter in unweighted soleus muscle of normal and STZ-induced diabetic rats." Am.J.Physiol.264. E301-E307 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Katagiri H et al: "The role of tryptophan 388 of GLUT1 glucose transporter on glucose transport activity and photoaffinity-labelling with forskolin." Biochemical J.291. 861-867 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Asano T et al.: "The role of N-glycosylation in the targeting and stability of GLUT1 glucose transporter." FEBS lett. 324. 258-261 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Inukai K et al.: "Cloning and increased expression with fructose feeding of rat jejunal GLUT5." Endocrinology. 138. 2009-2014 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takata K et al.: "Mammalian sugar transporters:Their localization and link to cellular functions." Acta Histochem Cytochem. 26. 165-178 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 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(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ishihara H.et al.: "Expression of GLUT4 glucose transporter in unweighted soleus muscle of normal and STZ-induced diabetic rats." Am.J.Physiol.264. E301-E307 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Katagiri H.et al.: "The role of tryptophan 388 of GLUT1 glucose transporter on glucose transport activity and photoaffinity-labelling with forskolin." Biochemical J. 291. 861-867 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Asano T.et al.: "The role of N-glycosylation in the targeting and stability of GLUT1 glucose transporter." FEBS lett. 324. 258-261 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Inukai K.et al.: "Cloning and increased expression with fructose feeding of rat jejunal GLUT5." Endocrinology. 138. 2009-2014 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takata K.et al.: "Mammalian sugar transporters : Their localization and link to cellular functions." Acta Histochem Cytochem. 26. 165-178 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 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
      1993 Final Research Report Summary
  • [Publications] Ishihara H et al.: "Expression of GLUT4 glucose transporter in unweighted soleus muscle of normal and STZ-induced diabetic rats." Am.J.Physiol.264. E301-E307 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Katagiri H et al: "The role of tryptophan 388 of GLUT1 glucose transporter on glucose transport activity and photoaffinity-labelling with forskolin." Biochemical J.291. 861-867 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Asano T et al.: "The role of N-glycosylation in the targeting and stability of GLUT1 glucose transporter." FEBS lett. 324. 258-261 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Inukai K et al.: "Cloning and increased expression with fructose feeding of rat jejunal GLUT5." Endocrinology. 138. 2009-2014 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takata K et al.: "Mammalian sugar transporters:Their localization and link to cellular functions." Acta Histochem Cytochem. 26. 165-178 (1993)

    • Related Report
      1993 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
      1993 Annual Research Report
  • [Publications] Asano,T.: "Up-regulation of GLUT2 mRNA by glucose,mannose,and fructose in isolated rat hepatocytes." Diabetes. 41. 22-25 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shibasaki,Y.: "Two glucose transporter isoforms are sorted differentially and are expressed in distinct cellular compartments." Biochem.J.281. 829-834 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Asano,T.: "Glucose increases the papain susceptibility of GLUT1 glucose transporter" FEBS letters. 298. 129-132 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Lin,J-L.: "Deletion of C-terminal 12 amino acids of GLUT1 protein does not abolish glucose transport activity." Biochem Biophys Res Commun.184. 865-870 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Asano,T.: "Domains responsible for differential targeting of glucose transporter isoforms" J.Biol.Chem.267. 19636-19641 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Katagiri,H.: "Replacement of intracellular C-terminal domain of GLUT1 glucose transporter with that of GLUT2 increases Vmax and Km of transport activity." J.Biol.Chem.267. 22550-22555 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Asano,T.: "Characterization of GLUT3 protein expressed in Chinese hamster ovary cells" Biochem.J. 288. 189-193 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Morita Y.: "Expression and possible function of glucose transporter protein GLUT1 during preimplantation mouse development from oocytes to blastocysts" Biochem Biophys Res Commun. 188. 8-15 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Oka,Y.: "Expression of glucose transporter isoforms with aging" Gerontology. 38. 3-9 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Oka,Y.: "Expression of glucose transporter isoforms in atrophied and enlarged muscle." Med.Sport Sci.37. 84-90 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Katagiri,H.: "Nonsense mutation of the glucokinase gene in late-onset non-insulin dependent diabetes mellitus." Lancet. 340. 1316-1317 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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