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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)
嶺尾 郁夫  大阪大学, 医学部, 助手 (40243240)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1992: ¥3,900,000 (Direct Cost: ¥3,900,000)
KeywordsNon-insulin-dependent diabetes mellitus / Glycolysis / Gluconeogenesis / Insulin action / Otsuka Long-Evans Tokushima Fatty rat / Phosphofructokinase / Promoter / Insulin resistance / OLETF / グルコキナーゼ / ピルビン酸キナーゼ / 糖尿病 / 遺伝子調節 / 遺伝子クローニング
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.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 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
    • Related Report
      1994 Final Research Report Summary
  • [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
    • Related Report
      1994 Final Research Report Summary
  • [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
    • Related Report
      1994 Final Research Report Summary
  • [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
    • Related Report
      1994 Final Research Report Summary
  • [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
    • Related Report
      1994 Final Research Report Summary
  • [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
    • Related Report
      1994 Final Research Report Summary
  • [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
    • Related Report
      1994 Final Research Report Summary
  • [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
    • Related Report
      1994 Final Research Report Summary
  • [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
    • Related Report
      1994 Final Research Report Summary
  • [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
    • Related Report
      1994 Final Research Report Summary
  • [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
    • Related Report
      1994 Final Research Report Summary
  • [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
    • Related Report
      1994 Final Research Report Summary
  • [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
    • Related Report
      1994 Final Research Report Summary
  • [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
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakajima,H.etal: "Expression of mouse phospho fructokinase-M gene alternative transcripts:evidence for the conserved two-promoter system" Biochem.J.303. 449-453 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hamaguchi,T.etal: "A new variant of muscle phosphofructokinase deficiency in a Japanese case with abnormal RNA splicing" Biochem.Biophys.Res.Commun.202. 444-449 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Waguri,M.etal: "Occurrence of IDDM during interferon therapy for chronic viral hepatitis" Diabetes Res.Clin.Pract.23. 33-36 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Itoh,N.etal.: "No detectable cytomegalovirus and Epstein-Barr virus genomes in the pancreas of newly onset IDDM patients" Diabetologia. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Ono,A.etal.: "Glucose infusion paradoxically accelerates degradation of adenine nucleotide in working muscle of patients with glycogen storage desease Type VII." Neurology. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Tamura,S.etal.: "Effects of glucagon on urinary excretion of urea and on plasma ammonia level in argininosuccinate sgnthetase deficiency" J.Gastroenterol.29. 31-34 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 河野典夫: "Annual Review 内分泌代謝1994" 中外医学社, 287 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 河野典夫: "最新内科学大系" 中山書店(印刷中),

    • Related Report
      1994 Annual Research Report
  • [Publications] Itoh,N.: "Mononuclear cell infiltration and its relation to the expression of MHC antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed IDDM patients." J.Clin.Invest.92. 2313-2322 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yamagata,K.: "Overexpression of HLA class I antigen reduces insulin secretion in pancreatic β cells(RINm5F)" Res.Commun.Chem.Pathol.Pharmacol.81. 299-308 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Waguri,M.: "Occurrence of IDDM during interferon therapy for chronic viral hepatitis" Diabetes Res.Clin.Pract.(in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Namba,M.: "Clinical evaluation of biosynthetic glucagon treatment for recovery from hypoglycemia developed in diabetic patients" Diabetes Res.Clin.Pract.19. 133-138 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Asakawa,H.: "Effects of tumor necrosis factor α on the thyroid peroxidase content,DR antigen expression,and number of microvilli in cultured human thyrocytes." Biomed.Res.14. 5-11 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 堀田紀久子: "NIDDMモデルラットOLETFにおける肝糖代謝酵素の発現" 糖尿病. (印刷中).

    • Related Report
      1993 Annual Research Report
  • [Publications] 河野典夫: "神経疾患の遺伝学" 金原出版, 508 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 河野典夫: "新臨床内科学" 医学書院, 1646 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] N.Itoh: "Transthyretin (prealbumin) in the pancreas and sera of newly diagnosed type I (insulin-dependent) diabetic patients." J.Clin. Endocrinol. Metab.74. 1372-1377 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] C.Nakagawa: "Retrovirus gag protein p30 in the islets of non-obese diabetic mice: relevance for pathogenesis of diabetes mellitus." Diabetologia. 35. 614-618 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Matsumura: "Glucagonlike peptide-1(7-36) amide suppresses glucagon secretion and decreases cyclic AMP concentration in cultured In-R1-G9 cells." Biochem. Biophys. Res. Commun.186. 503-508 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H.Nakajima: "An alternative,non-isotopic protocol of PCR-mediated allele-specific oligonucleotide analysis for the detection of a point mutation." Res. Commun. Chem. Pathol. Pharmacol.79. 3-10 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Jinnai: "Glycogenosis type V (McArdle′s disease) with hyperuricemia. A case report and clinical investigation." Eur. Neurol.

    • Related Report
      1992 Annual Research Report
  • [Publications] 河野 典夫: "細胞内外のインスリン抵抗性要因" 糖尿病記録号 1991. 1. 157-160 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 河野 典夫: "最新内科学大系 第51巻 先天性代謝異常" 中山書店, 380 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 河野 典夫: "生化学実験講座 第15巻 代謝異常" 東京化学同人, 378 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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