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IDENTIFICATION OF THE GENES INVOLVED IN GLUCOSE-STIMULATED INSULIN SECRETION

Research Project

Project/Area Number 07557168
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Human genetics
Research InstitutionGUNMA UNIVERSITY

Principal Investigator

TAKEDA Jun  GUNMA UNIVERSITY INSTITUTE FOR MOLECULAR AND CELLULAR REGULATION,PROFESSOR, 生体調節研究所, 教授 (40270855)

Co-Investigator(Kenkyū-buntansha) IZUMI Tetsurou  GUNMA UNIVERSITY INSTITUTE FOR MOLECULAR AND CELLULAR REGULATION,ASSOCIATE PROFE, 生体調節研究所, 助教授 (00212952)
TAKEUCHI Toshiyuki  GUNMA UNIVERSITY INSTITUTE FOR MOLECULAR AND CELLULAR REGULATION,PROFESSOR, 生体調節研究所, 教授 (00109977)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥16,300,000 (Direct Cost: ¥16,300,000)
Fiscal Year 1997: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1996: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1995: ¥9,300,000 (Direct Cost: ¥9,300,000)
KeywordsGLUCOKINASE / GENOME DATABASE / インスリン分泌 / グルコースセンサー
Research Abstract

RIN cells are originated from rat pancreatic beta cells. After multiple rounds of passages, they lose sensitivity to glucose stimulation and subsequent insulin secretion, at least in part through diminished expression of glucokinase. Glucokinase is thought to play a major role as a glucose sensor in pancreatic beta cells. In this study, we attempted to identify genes involved in glucose-stimulated insulin secretion by the method of mRNA differential display using glucokinase-overexpressed RIN cells and untreated cells. We identified thirteen differentially expressed genes in this process. Among these genes, the expression levels of five genes were increased by overexpression of glucokinase. They include genes encoding L-type pyruvate kinase, mitochondrion, and uroporphyrinogen decarboxyrase, and unknown genes. The genes encoding calmodulin and glycosylphosphatidyl -inositol-anchored protein were down regulated. Interestingly, calmodulin has been shown to decrease insulin secretion in mouse pancreatic beta cells when overexpressed. Furthemore, the expression of L-type pyruvate kinase in liver is known to be regulated by insulin in a similar manner to glucokinase. These results suggest that the genes identified in this study might be associated with the glucose-sensing mechanism via interaction with glucokinase in pancreatic beta cells and may play crucial roles insulin secretion.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] K.Yamagata et al.: "Searching for NIDDM susceptibility genes:studies of genes with triplet repeats expressed in skeletal muscle" Diabetologia. 39. 725-730 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] D.Wasserman et al.: "Molecular analysis of the fructose transporter gene(GLUT5) in isolated fructose malabsorption." J.Clin.Invest.98. 2398-2402 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Yamagata et al.: "Mutaions in the hepatocyte nuclear factor 1α gene in maturity-onset diabetes of the young(MODY3)." Nature. 384. 455-458 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Yamada et al.: "Mutations in the hepatocyte nuclear factor-1α gena(MODY3)are not a major cause of late-onset NIDDM in Japanese." Diabetes. 46. 1512-1513 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Yamada et al.: "Identification of mutations in the hepatocyte nuclear factor-1α(HNF-1α)gene in Japanese subjiects with IDDM." Diabetes. 46. 1643-1647 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Nishigori et al.: "Identification and characterization of the gene encoding a second proteolipid subunit of humanvacuolar H^+-ATPase(ATP6F)" Genomics. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Yamagata et al.: "Searching for NIDDM susceptibility genes : studies of genes with triplet repeats expressed in skeletal muscle." Diabetologia. 39. 725-730 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] D.Wasserman et al.: "Molecular analysis of the fructose transporter gene (GLUT5) in isolated fructose malabsorption." J.Clin.Invest.98. 2398-2402 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Yamagata et al: "Mutaions in the hepatocyte nuclear factor 1 alpha gene in maturity-onset diabetes of the young (MODY3)" Nature. 384. 455-458 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Yamada et al.: "Mutations in the hepatocyte unclear factor-1alpha gene (MODY3) are not a major cause of late-onset NIDDM in Japanese." Diabetes. 46. 1512-1513 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Yamada et al.: "Identification of mutations in the hepatocyte unclear factor-1alpha (HNF-1alpha) gene in Japanese subjects with IDDM." Diabetes. 46. 1643-1647 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Nishigori et al.: "Identification and characterization of the gene encoding a second proteolipid subunit of human vacuolar H^+-ATPase (ATP6F)." Genomics. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Yamagata et al.: "Searching for NIDDM susceptibility genes:studies of genes with triplet repeats expressed in skeletal muscle." Diabetologia. 39. 725-730 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] D.Wasserman et al.: "Molecular analysis of the fructose transporter gene(GLUT5)in isolated fructose malabsorption." J.Clin.Invest.98. 2398-2402 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Yamagata et al.: "Mutaions in the hepatocyte nuclear factor 1 alpha gene in maturity-onset diabetes of the young(MODY3)." Nature. 384. 455-458 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Yamada et al.: "Mutations in the hepatocyte nuclear factor-1α gene(MODY3)are not a major cause of late-onset NIDDM in Japanese." Diabetes. 46. 1512-1513 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Yamada et al.: "Identification of mutations in the hepatocyte nuclear factor-1α(HNF-1α)gene in Japanese subjects with IDDM." Diabetes. 46. 1643-1647 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Nishigori et al.: "Identification and characterization of the gene encoding a second proteolipid subunit of human vacuolar H^+-ATPase(ATP6F)." Genomics. in press. (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Yamagata et al: "Mutaions in the hepatic nuclear factor-1αgene in maturity-onset diabetes of the young (MODY3)." Nature. 384. 455-458 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Yamagata et al.: "Searching for NIDDM susceptibility genes : studies of genes with triplet repeats expressed in skeletal muscle." Diabetologia. 39. 725-730 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] D.Wasserman et al.: "Molecular analysis of the fructose transporter gene (GLUT5) in isolated fructose malabsorption." J.Clin.Invest.98. 2398-2402 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] A.Hino et al.: "Increased expression of endothelin B receptor mRNA following subatachnoid hemorrhage in monkeys." J.Cerebral.Biood Flow Metab.16. 688-697 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] A.Hino et al.: "Changes in endothelial nitric oxide synthase mRNA during vasospasm after subarachnoid hemorrhage in monkeys." Neurosurgery. 39. 562-568 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] R.Hromas et al.: "Exodus,a novel chemokine that inhibits proliferation of hematopoietic progenitors and HIV." Blood. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y. Tokuyama and J. Takeda.: "Use of ^<33>P increase the sensitivity and specificity of mRNA differential display" Bio Techniques. 18. 424-425 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] J. Takeda, et al.: "Localization of human somatostatin receptor gene (SSTR5) to chromosome band 16q13.3 by fluorescence in situ hybridization." Genomics. 26. 638-639 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] M.R.El-Maghrabi, et al.: "Human fructose-1,6-bisphosphatase gene (FBP1) : Exon-intron organization, localization to chromosome bands 9q-22.2-q22.3, and mutation screening in subjects with frucotose-1, 6-bisphosphatase deficiency." Genomics. 27. 520-525 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] J. Takeda, et al.: "Chromosomal assignment and tissue distribution of novel expressed sequence tags from a human pancreatic islet cDNA library." Genomics. 29. 276-281 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y. Tokuyama, et al.: "Evolution of β-cell dysfunction in the male zucker diabetic fatty rat." Diabetes. 44. 1447-1457 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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