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1994 Fiscal Year Final Research Report Summary

Gene expression of glycolytic and gluconeogenic enzymes and its derangement in diabetes mellitus

Research Project

Project/Area Number 04454561
Research Category

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

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

Principal Investigator

KONO Norio  Osaka Univ, Faculty of Medicine, Professor, 医学部, 教授 (30093412)

Co-Investigator(Kenkyū-buntansha) KUWAJIMA Masamichi  Osaka Univ, Faculty of Medicine, Assist Prof., 医学部, 講師 (00205262)
HANAFUSA Toshiaki  Osaka Univ, Faculty of Medicine, Assist Prof., 医学部, 講師 (60164886)
NAMBA Mitsuyoshi  Osaka Univ, Faculty of Medicine, Instructor, 医学部, 助手 (00183533)
NAKAJIMA Hiromu  Osaka Univ, Faculty of Medicine, Instructor, 医学部, 助手 (50252680)
Project Period (FY) 1992 – 1994
KeywordsNon-insulin-dependent diabetes mellitus / Glycolysis / Gluconeogenesis / Insulin action / Otsuka Long-Evans Tokushima Fatty rat / Phosphofructokinase / Promoter / Insulin resistance
Research Abstract

Phosphofructokinase (PFK) is a regulatory enzyme in glycolysis. Three isozymes are known as muscle (M), liver (L) and platelet (P) types. We compared human PFK-M and-L genes and various species M and L genes. The results suggest that the establishment of isozyme genes preceded the speciation of animal species during evolution.
Human PFK-M gene has tissue-specific two promoter system and slternative splicing mechanism. Similar promoter and expression system is evolutionally conserved in mouse PFK-M gene. Total PFK-M mRNA was decreased in cardiac and skeletal muscles of ketotic diabetic mice. This suggests that insulin regulates PFK-M gene expression at the level of transcription and/or splicing. Cultured islet cell tumor exhibited three isozyme mRNAs, being predominant L-type.
This indicates the significant role of PFK-L in the regulation of insulin secretion from pancreatic beta cells.
We disclosed two novel mutations in the PFK-M gene in Japanese patients with glycogenosis VII.There are three different mutations in three Japanese families, which is contrasted with a limited mumber of mutations common to the affected families in other racial population.
OLETF rats are animal model of insulin resistant diabetes. Increased activities and mRNA levels of both glycolytic and gluconeogenic regulatory enzymes in liver may be the reflection of expression of insulin resistance in the gluconeogenic enzymes. Defect of intracellular signal transduction of insulin or anti-insulin action of unidentified substance is possibly involved in the pathogenesis of insulin resistance in liver.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] N.Itoh et al: "Transthyretin(prealbumin)in the pancreas and sera of newly diagnosed typeI(insulin-dependent)diabetic patients" J.Clin.Endocrinol.Metab.74. 1372-1377 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Itoh et al: "Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pacreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients" J.Clin.Invest.92. 2313-2322 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Waguri et al: "Occurrence of IDDM during interferon therapy for chronic viral hepatitis" Diabetes Res.Clin.Pract.23. 33-36 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Nakajima et al: "An alternate nonisotopic technique of PCR-mediated allete-specific oligonucleotide analysis for the detection of a point mutation" Res.Commun.Chem.Pathol.Pharmacol.79. 3-10 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Nakajima et al: "Expression of mouse phosphofructokinase M gene alternative transcripts:evidence for the conserved two-promoter system" Biochem.J.303. 449-453 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Hamaguchi et al: "A new variant of muscle phosphofructokinase deficiency in a Japanese case with abnormal RNA splicing" Biochem.Biophys.Res.Commun.202. 444-449 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 河野典夫: "Annual Reviw 内分泌代謝1994" 中外医学社, 287 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 河野典夫: "最新内科学体系" 中山書店(印刷中),

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Itoh et al: "Transthyretin (prealbumin) in the pancreas and sera newly diagnosed typel 1 (insulin-dependent) diabetic patients" J.Clin.Endocrinol.Metab.74 (6). 1372-1377 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Itoh et al: "Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pacreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients." J.Clin.Invest. 92 (5). 2313-2322 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Waguri et al: "Occurrence of IDDM during interferon therapy for chronic viral hepatitis." Diabetes Res.Clin.Pract.23. 33-36 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Nakajima et al: "An alternate nonisotopic technique of PCR-mediated allele-specific oligonucleotide analysis for the detection of a point mutation." Res.Commun.Chem.Pathol Pharmacol. 79 (1). 3-10 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Nakajima et al: "Expression of mouse phosphofructokinase-M gene alternative transcripts : evidence for the conserved two-promoter system." Biochem.J.303. 449-453 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Hamaguchi et al: "A new variant of muscle phosphofructokinase deficiency in a Japanese case with abnormal RNA splicing." Biochem.Biophys.Res.Commun. 202 (1). 444-449 (1994)

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

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Published: 1996-04-15  

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