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1991 Fiscal Year Final Research Report Summary

Studies on molecular mechanism of etiology of diabetes mellitus

Research Project

Project/Area Number 02671093
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionKyoto University

Principal Investigator

SEINO Yutaka  Kyoto University, Dept. of Medicine, Associate Prof., 医学部, 助教授 (40030986)

Project Period (FY) 1990 – 1991
KeywordsDiabetes mellitus / obesity / glucose transporter (GLUT) / gene expression / mRNA / islet / liver / nuscle
Research Abstract

In order to investigate the regulation of glucose transporter gene expression in the altered metabolic conditions of diabetes, we have measured MRNA levels encoding GLUT4 in the liver and GLUT4 in the gastrocnemius muscle from various insulin resistant animal models, including Zucker fatty, Wistar fatty, and streptozocin(STZ)-treated diabetic rats. Northern blot analysis revealed that GLUT2 MRNA levels were significantly(P<0.001)elevated in 14 wk Zucker fatty and Wistar fatty rats relative to lean littermates but were similar in these two groups at 5 wk of age. Furthermore, there was significant increase(P<0.01)in GLUT2 MRNA levels in STZ diabetic rats at 3 wk after treatment. GLUT4 MRNA levels were not significantly different between control and insulin resistant rats in all animal models. These results indicate that neither hyperinsulinemia nor hyperglycemia affects GLUT4 MRNA levels in the muscle. However, GLUT2 MRNA levels in the liver were elevated in obesity and diabetes, althoug … More h this regulatory event occurred independently from circulating insulin or glucose concentrations. On the other hand, previous studies revealed that rat islets express the GLUT2-liver facilitative glucose transporter isoform, a glucose carrier with a low affinity for glucose but a high capacity for glucose transport. These studies indicated the presence of a second glucose transporter in rat islets ; however, they did not indicate to which of the five known facilitative glucose transporters it corresponded. In this study, we isolated RNA from rat islets of Langerhans and confirmed the presence of GLUT2 MRNA. In addition, we present data indicating that the second isoform expressed in islets is the GLUTI-erythrocyte isoform. The effect of culturing islets in 5.5, 8.3 or 11.1 mM glucose on the levels of GLUT1 and GLUT2 MRNA also was examined. The levels of GLUTI and GLUT2 MRNA were two- and threefold higher, respectively, in islets cultured for 24 h in 11.1 mM glucose compared with those incubated in the presence of 5.5 mM glucose. Therefore, the previously observed increase in GLUT2 MRNA levels in the islets of rats made hyperglycemic by chronic infusion of glucose can be mimicked in vitro, implying that glucose regulates GLUT2 MRNA expression. Less

  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Y.Yamada,Y.Seino,et al.: "Increase in liver glucose transporter mRNA levels during rat liver regeneration" Biochem Biophys Res Commun. 168. 1274-1279 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Yamamoto,Y.Seino,et al.: "Over-expression of facilitative glucose transporter genes in human cancer" Biochem Biophys Res Commun. 170. 223-230 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Yano,Y.Seino,et al.: "Tissue distribution and species difference of the brain type glucose transporter (GLUT3)" Biochem Biophys Res Commun. 174. 470-474 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Yamamto,Y.Seino,et al.: "Liver and muscle-fat type glucose transporter gene expression in obese and diabetic rats" Biochem Biophys Res Commun. 175. 995-1002 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Yasuda,Y.Seino,et al.: "Expression of GLUT1 and GLUT2 glucose transporter isoforms in rat islets of langerhans and their regulation by glucose" Diabetes. 41. 76-81 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Inagaki,Y.Seino,et al.: "c-Jun represses the human insulin promoter artivity that depends on multiple cAMP response elements" Proc Natl Acad Sci USA.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Ozono, Y. Seino, et al.: "1, 25-Dihydroxyvitamin D3 enhances the effect of refeeding on steady state preproinsulin messenger rebonucleic acid levels in rats" Endocrinology. 126(4). 2041-2045 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Yamada, Y. Seino, et al.: "Increase in liver glucose transporter mRNA levels during rat liver regeneration" Biochem Biophys Res Commun. 168(3). 1274-1279 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Yamamoto, Y. Seino, et al.: "Over-expression of facilitative glucose transporter genes in human cancer" Biochem Biophys Res Commun. 170(1). 223-230 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Seino, et al.: "C-terminal peptide of the GIP precursor and pancreastatin fragments on insulin secretion from isolated rat islets." Biomed Res. 11(4). 283-286 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] G. Koh, Y. Seino, et al.: "Importance of impaired insulin gene expression in the occurrence of diabetes in obese rats" Diabetes. 39(9). 1050-1056 (1990)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-03-16  

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