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Mechanism of Action of Insulin-like Growth Factor

Research Project

Project/Area Number 63570525
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionGunma University (1990)
The University of Tokyo (1988-1989)

Principal Investigator

KOJIMA Itaru (1989-1990)  Professor, Institute of Endocrinology, Gunma University, 内分泌研究所, 教授 (60143492)

貴田岡 正史 (1988)  東京大学, 医学部, 助手 (20153091)

Co-Investigator(Kenkyū-buntansha) KITAOKA Masafumi  Director, Endocrine Clinic, Showa Hospital, 内分泌代謝科, 医長 (20153091)
小島 至  東京厚生年金病院, 内科, 医長 (60143492)
Project Period (FY) 1988 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1990: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1989: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1988: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsInsulin-like Growth Factor / Growth / Calcium / Diacylglycerol / Cell-cycle / G蛋白 / ジアシルグリセロール
Research Abstract

Insulin-like gowth factor-I (IGF-I) is a potent growth factor which plays a pivotal role in somatic growth. We studied the mechanism of action of IGF-I using Balb/c 3T3 cells as a model system. In these cells, IGF-I promotes cell-cycle progression. In doing so, IGF-I exerts its action in a cell-cycle-dependent manner. Thus, IGF-I promotes cell-cycle progression when quiescent cells are pretreated with platelet-derived growth factor (PDGF) and epidermal growth factor (EGF). We studied the action of IGF-I using IGF-I-responsive cells, which we termed primed competent cells. In these cells, IGF-I induces sustained increase in calcium entry. This is brought about by an activation of IGF-I-sensitive calcium-permeable cation channel. When calcium entry is blocked, IGF-I is not capable of stimulating DNA synthesis. In addition, pharmacological stimulation of calcium entry results in an increase in DNA synthesis. These results let us to propose that calcium entry is an intracellular message of the mitogenic action of IGF-I. It should be mentioned that DNA synthesis is augmented in primed competent cells whereas stimulation of calcium entry does not affect DNA synthesis in quiescent cells. These results indicate that calcium-sensing machinery does not operate in quiescent cells. In addition to stimulation of calcium entry, IGF-I increases diacylglycerol (DAG) in primed competent cells. There are at least three sources of diacylglycerol. First, glycosylphosphatidylinositol, known to be a precursor of insulin-mediator inositolglycan, is hydrolyzed by IGF-I. Second, phosphatidylcholine is hydrolyzed by phospholipase C, and finally, IGF-I stimulates de novo synthesis of diacylglycerol. As a result, IGF-I causes sustained elevation of cellular DAG content. It remains unsolved whether protein kinase C is activated continuously by IGF-I.

Report

(4 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • 1988 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Kojima,I., Matsunaga,H., Kurokawa,K., Ogata,E. and Nishimoto,I: "Calcium Influx : An Intracellular Message of the Mitogeme Action of Insulinーlike Growth FactorーI" J.Biol. Chem.262. 16561-16567 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Matsunage,H., Nishimoto,I., Kojima,I., Yamashita,N., Kurokawa,K. and Ogata,E.: "Activation of a Calcium Permeable Cation Channel by Insulinーlike Growth FactorーII in Balb/c 3T3 Cells." Am. J. Physiol.255. C442-C446 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hata,Y., Ogata,E. and KoJima,I.: "Plateletーderived Growth Factor Stimulates Synthesis if 1.2ーDiacylglycerol in Balb/c 3T3 Cells." Biochem.J.262. 947-952 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kojima,I., Kitaoka,M. and Ogata,E.: "Guaniue Nucleotides Modify Calcium Entry Inducel by Insulinーlike Growth FactorーI." FEBS Lett.258. 150-152 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kojima,I., kitaka,M. and Ogata,E.: "Studies on the Cellーcycle Dependeuce of the actions of Insulinーlike Growth FactorーI in Balb/c 3T3 Cells." J. Cell. Physiol.143. 529-533 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kojima,I., Kitaoka,M. and Ogata,E.: "Insulinーlike Growth FactorーI Stimulates Production of Diacylglycerol Viu Multiple Pathways in Balb/c 3T3 Cells." J.Biol.Chem.265. 16846-16850

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 岡田 善男編 小島 至,野瀬 清,豊島 久真男: "岩波講座.分子生物科学 細胞の増え方" 岩波書店,

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kojima, I. Matsunaga, H., Kurokawa, K., and Ogata, E.: "Calcium Influx : An Intracellular Message of the Mitogenic Action of Insulin-like Growth Factor-I" J. Biol. Chem.263. 16561-16567

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Matsunaga, H., Nishimoto, I., Kojima, I., Yamashita, N., Kurokawa, K. and Ogata, E.: "Activation of a Calcium-permeable Cation Channel by Insulin-like Growth Factor in Balb/c 3T3 Cells" Am. J. Physiol.255. C442-C446

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kojima, I., Nishimoto, I., Iiri, T., Ogata, E. and Rosenfeld, R.: "Evidence That Type II IGF Receptor Is Coupled to Calcium Gating System." Biochem. Biophys. Res. Comm.154. 9-19 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hata, Y., Ogat, E. and Kojima, I.: "Platelet-derived Growth Factor Stimulates Synthesis of 1, 2-Diacylglycerol in Balb/c 3T3 Cells." Biochem. J.262. 947-952

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kojima, I., Kitaoka, M. and Ogata, E.: "Guanine Nucleotides Modify Calcium Entry Induced by Insulin-like Growth Factor-I." FEBS Lett.258. 150-152

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kojima, I., Kitaoka, M., and Ogata, E.: "Studies on the Cell-cycle Dependency of the Actions of Insulin-like Growth Factor-I in Balb/c 3T3 Cells." J. Cell. Physiol.143. 529-533

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kojima, I., Kitaoka, M. and Ogata, E.: "Insulin-like Growth Factor-I Stimulates Production of Diacylglycerol in Balb/c 3T3 Cells." J. Biol. Chem.265. 16846-16850

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kojima,I.,Kitaoka,M.and Ogata,E.: "Studies on the Cellーcycle Dependency of the Actions of Insulinーlike Growth FactorーI in Balb/c 3T3 Cells." J.Cell.Physiol.143. 529-533 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kojima,I.,Kitaoka,M.and Ogata,E.: "Insulinーlike Growth FactorーI Stimulates Production of Diacylglycerol in Balb/c 3T3 Cells." J.Biol.Chem.265. 16846-16850 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Itaru Kojima,Masafumi Kitaoka,Etsuro Ogata: "Guanine Nucleotides Modify Calcium Evitry Induced by Insulin-like Growth Factor-I" FEBS Letters.

    • Related Report
      1989 Annual Research Report
  • [Publications] Itaru Kojima,Masafumi Kitaoka,Etsuro Ogata: "Studies on the Cell-cycle Dependency of the Action of Insulin-like Growth Factor-I"

    • Related Report
      1989 Annual Research Report
  • [Publications] Kojima I.;,Nishimoto,I.;Iiri,T.;Ogata,E,;Rosenfeld,R.: Biochem.Biophys.Res.Commun. 154. 9-19 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Kojima,I.;Matsunaga,H.;Kurokawa,K;Ogata,E,;Nishimoto,I.: J.Biol.Chem. 263. 16561-16567 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Matsunaga,H;Nishimoto,I.;Kojima,I,;Yamashita,N,;Kurokawa,K;OgaTa,E.: Am.J.Physiol. 255. C442-C446 (1988)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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