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Alteratin of islet glycolysis in diabetic state

Research Project

Project/Area Number 02671098
Research Category

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

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

Principal Investigator

NISHIKAWA Yoshiro  Osaka University Medical School, assistant Professor, 医学部, 助手 (10218141)

Co-Investigator(Kenkyū-buntansha) KAWACHI Masanori  Osaka University Medical School, Research associate, 医学部附属病院, 医員
宮川 潤一郎  大阪大学, 医学部附属病院, 医員
SHIMIZU Takao  Osaka University Medical School, assistant Professor, 医学部, 助手
KONO Norio  Osaka University Medical School, associate Professor, 医学部, 助教授 (30093412)
MIYAGAWA Jun-ichoro  Osaka University Medical School, Research associate
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1991: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsDiabetes mellitus / Glucokinase / Phosphofructokinase / Liver / Islet / Glycolysis / ピルビン酸キナ-ゼ
Research Abstract

Islet glycolysis plays an important role in the regulation of glucose-stimulated insulhi release. Regulation of islet glycolysis is complicated by the dual glucose phosphorylation system : glucokinase and hexokinase. Glucokinase activity depends mostly on the level of the substrates. On the other hand, hexokinase activity is controlled by the activity of phosphofructokinase through the level of glucose 6-phosphate. Recently, glucose-stimulated insulin release was reported to be impaired in NIDDM. Glucagon-. or arginine-stimulated insulin release does not. These observations indicates that islet glycolytic system, which is proposed to regulate insulin release, may be impaired. In this study, we aimed to study. the alteration of islet glycolysis. -First, we prepared the cDNA probe of liver type phosphofructokinase. Using this probe and the cDNA probe of muscle type phosphofructokinase, we analyzed tissue distribution of these two types of phosphofructokinase. Using Northern analysis and … More PCR technique, most tissue including cultured b cells expressed both types of phosphofructokinase mRNA. Then, we analyzed muscle phosphofructokinase gene. It spans about 30kb, and has 24 exons. Its gene contains at least two premotor regions, facilitating the expression of the heterogeneous gene transcripts in tissue specific manner. Next, we analyzed the alteration of expression of glucokinase, phosphofructokinase, and pyruvate kinase mRNA in the rat liver. Rat liver contains glucokinase and liver type phosphofrutokinase as b cells do. Fasting decreased glucokinase mRNA level and refeeding restored its level quite rapidly. mRNA level of pyruvate kinase was also decreased after fasting. Its restoration by refeeding was slow. On the contrary to these two enzymes, mRNA level of phosphofructokinase was not altered either by fasting or by refeeding. Then, we studied the effect of insulin in the streptozotocin-treated diabetic rats. The effect of diabetic state and of the insulin treatment was resembled to that of fasting-refeeding. The increase in glucokinase mRNA after insulin injection was rapid. The restoration in pyruvate kinase mRNA was slow. Phosphofructokinase mRNA was not altered in these treatment. As shown in this study, the regulation of these enzymes were quite different. Less

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] T.Hanafusa: "Examination of islets in the pancreas biopsy specimens from newly diagnosed type 1(insulin-dependent)diabetic patients." Diabetologia. 33. 105-111 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H.Nakajima: "Evidence for alternative RNA splicing and possible alternative promoters in the human muscle phosphofructokinase gene at the 5'untranslated region." Biochem Biophys Res Commun. 166. 637-641 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H.Nakajima: "Tissue specificity in expression and alternative RNA splicing of human phosphofructokinase-M and -L genes." Biochem Biophys Res Commun. 173. 1317-1321 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H.Nakajima: "Genetic defect in muslce phosphofructokinase deficiency: Abnormal splicing of the muscle phosphofructokinase gene due to a point mutation at the 5'-splice site." J.Biol Chem. 265. 9392-9395 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T.Yamasaki: "Structure of the entire human muscle phosphofructokinase-encoding gene: A two-promoter system." Gene. 104. 277-282 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] K.Hotta: "Rat liver type phosphofructokinase mRNA.Structure,tissue distribution and regulation." Eur.J.Biochem.202. 293-298 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Hanafusa: "Examination of islets in the pancreas biopsy specimens from newly diagnosed type 1 (insulin-dependent) diabetic patients." Diabetologia. 33(2). 105-111 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Nakajima: "Evidence for alternative RNA splicing and possible alternative promoters in the human muscle phosphofructokinase gene at the 5' untranslated region." Biochemical Biophys Res Commun. 166(2). 637-641 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Nakajima: "Genetic defect in muslce phospofructokinase deficiency : Abnormal splicing of the muscle phosphofructokinase gene due to a point mutation at the 5'-splice site." J Biol Chem. 265(16). 9392-9395 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] N. Kono: "Muscle glycogenoses." Inborn Metabolic Diseases : Diagnosis and treatment. Spriner-Verlag, Berlin. 89-94 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Nakajima: "Tissue specificity in expression and alternative RNA splicing of human phosphofructokinase-M and -L genes" Biochem Biophys Res Commun. 173(3). 1317-1321 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Yamasaki: "Structure of the entire human muscle phosphofructokinase-encoding gene : A two-promoter system." Gene. 104(2). 277-282 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] K. Hotta: "Rat liver type phosphofructokinase mRNA. Structer, tissue distribution and regulation." Eur J. Biochem.202. 293-298 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Nakajima: "A genetic defect in muscle phosphofructokinase deficiency, typical clinical entity presenting myogenic hyperuricemia." Human Purine & Pyrimidine Metabolism in Man VII. Plenum Publishing Co, New York and London.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T.Yamasaki: "Structure of the entire human muscle phosphofructokinaseーencoding gene:A twoーpromoter system." Gene. 104. 277-282 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Hotta: "Rat liver type phosphofructokinase mRNA. Structure,tissue distribution and regulation." Eur.J.Biochem.202. 293-298 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 清水 孝郎: "膵島b細胞グルコキナ-ゼ.グルコ-スセンサ-としての意義と最近の知見." 実験医学. 9. 398-403 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 清水 孝郎: "膵島解糖系とグルコ-スセンサ-" 内分泌学の進歩. 8. 198-210 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 中島 弘: "インスリン効果器官におけるホスホフルクトキナ-ゼ遺伝子の機能とその異常." 実験医学. 9. 465-470 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 中島 弘: "ホスホフルクトキナ-ゼM遺伝子における組織特異的なaltemative splicingの分析." プリン・ピリミジン代謝.

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Hanafusa: "Examination of islets in the pancreas biopsy speciments from newly dianosed typel (insulinーdependent) diabetic patients" Diabetologia. 33. 105-111 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] J.Miyagawa: "Preventive effect of a new immunosuppressant FKー506 on insulitis and diabetes in nonーobese diabetic mice" Diabetologia. 33. 503-505 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] H.Nakajima: "Evidence for alternaive RNA splicing and possible alternative promotors in the human muscle phosphofructokinase gene at the 5'untranslated region" Biochem Biophys Res Commun. 166. 637-641 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] H.Nakajima: "Tissue specificity in expression and alternative RNA splicing of human phosphofructokinase -M and -L genes" Biochem Biophys Res Commun. 173. 1317-1321 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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