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1997 Fiscal Year Final Research Report Summary

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
KeywordsGLUCOKINASE / GENOME DATABASE
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.

  • Research Products

    (12 results)

All Other

All Publications (12 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1999-03-16  

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