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Studies on negative regulation of insulin gene expression in non-pancreatic cells

Research Project

Project/Area Number 01570636
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

TSUDA Kinsuke  Kyoto University Assistance, 原子炉実験所, 助手 (10180001)

Co-Investigator(Kenkyū-buntansha) SEINO Yutaka  Kyoto University School of Medicine Assistant Professor, 医学部, 助教授 (40030986)
Project Period (FY) 1989 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1990: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1989: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsinsulin gene / cyclic AMP / GLUT / 糖輸送担体(Glut) / Glut 1 / CAT アッセイ / Hep G2 / HeLa / CAT活性 / エンハンサ-領域 / プロモ-タ-領域 / cAMP
Research Abstract

Insulin gene is expressed only in pancreatic B cells. So we have examined the effect of the 5'-branking region of the human insulin gene on its expression in non-pancreatic cells. The presence of the region containing the insulin gene enhancer (-339 to -169 bp) markedly repressed the promoter activity of the insulin gene. This suppressive phenomenon was restored by the addition of forsholin or dibutyryl cAMP suggesting that this region alone is not sufficient to repress completely insulin gene expression in the presence of extracellular stimuli which increase the intracellular cAMP level. These results show negative regulation of human insulin gene expression in non-pancreatu cells by these regions.
In order to clarify whether glucose transporter (GLUT) is glucosensor of pancreatic B cells, we have also studied GLUT. We isolated RNA from rat islets of Langerhans and confirmed the presence of GLUT2 mRNA and GLUT1 mRNA. And we also demonstrated glucose regulates GLUT2 mRNA expression. These results suggest GLUT2 may be glucosensor of pancreatic B cells.
By using Zucker fatty and Wistar fatty rats as models of obesity and diabetes, we showed that GLUT2 mRNA levels increase in both model rats and suggest that increassed GLUT2 mRNA levels may be associated with the development of obesity

Report

(3 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] J.TaKeda: "Negative regulation of human insulin gene expression by the 5′-flanking region in non-pancreatic cells" FEBS Letters. 247. 41-45 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Y.Seiro: "Expression of insulin and glucose transporter genes in obesity and diabetes" Progress in Obesity Research 1990. 371-374 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] H.Yaro: "Tissue distribution and species difference of the brain type glucose transporter(GLUT3)" Biochem Biophys Res Commun. 174. 470-477 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] K.Yasuda: "Expression of GLUT1 and GLUT2 glucose transporter isoformes 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
    • Related Report
      1990 Final Research Report Summary
  • [Publications] J. Takeda et al: "Negative regulation of human insulin gene expression by the 5'-flanking region in non-pancreatic cells." FEBS Letters. 247. 41-45 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Y. Seino et al: "Expression of insulin and glucose transporter genes in obesity and diabetes" Progress in Obesity Ressarch. 371-374 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] H. Yano et al: "Tissue distribution and speues difference of the brain type glucose transporter (GLUT3)" Biochem Biophys Res Commun. 174. 470-477 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] K. Yasuda 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(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Jun Takeda: "Negative regulation of human insulin gene expression by the 5′-flanking region in non-pancreatic cells" FEBS Letters. 247. 41-45 (1989)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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