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1998 Fiscal Year Final Research Report Summary

Mechanisms of Modulation of IGF's Action

Research Project

Project/Area Number 08044193
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field 応用微生物学・応用生物化学
Research InstitutionThe University of Tokyo

Principal Investigator

TAKAHASHI Shin-Ichiro  The University of Tokyo, Graduate School of Agriculture and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (00197146)

Co-Investigator(Kenkyū-buntansha) BOYAGES Stev  ウエストメッド病院, 内分泌学研究室, 研究室長
CONTI Marco  Stanfrod University, School of Medicine, Associate Professor, 医学部, 助教授
BAXTER Robert C.  Baxter Kolling Institute of Medical Research, Professor, 教授
CLEMMONS Dav  ノースキャロライナ大学, 医学部, 教授
VAN Wyk Juds  ノースキャロライナ大学, 医学部, 教授
WYK Judson J.Van  The University of North Carolina, School of Medicine, Professor
CLEMMONS David R.  The University of North Carolina, School of Medicine, Professor
BOYAGES Steven C.  Westmead Hospital, Department of Endocrinlogy, Department Chief
Project Period (FY) 1996 – 1998
KeywordsIGS-1 / IGFBP / IGF receptor / tropic hormone / cAMP / tyrosine kinase / cell growth cell differentiation / 細胞分化
Research Abstract

Recent evidence, derived from studies using knock-out or overexpression mice, indicates that insulinlike growth factors (IGFs) and/or their receptors are essential for the normal development and growth of mammals. Further, in many cell types IGFs have been shown to possess a variety of bioactivities, including the ability to induce cell proliferation and differentiaton, to inhibit cell apoptosis, and to maintain cell functio. IGFs circulates in the plasma and throughout the extracellular space as a complex with several specific binding proteins (IGFBPs). IGFBPs are believed at present to control half-lives of IGFs and modulate IGFs availability ; however, their physiological roles are still unclear. Despite the profuseness and diversity of IGFs bioactivities, the in vitro biological effects of IGFs are relatively weak and often are not demonstrable except in the presence of other hormones or growth factors. From this background, this study was undertaken to determine extracellular and … More intracellular mechanisms to modulate IGFs bioactivities in response to other hormones or growth factors, and different physiological conditions. Firstly, under various physiological conditions, we analyzed production of IGFs and IGFBPs interaction between IGFs and IGFBPs in serum, expression of IGF receptors. Our results suggested that expression of IGF/IGFBP/IGF receptors is regulated in different manners, resulting in reasonable IGFs bioactivities in response to each physiological situation. In additions, in endocrine cells, we demonstrated that tropic hormones prime cells to respond to IGF-I through cross-talk mechanisms of the intracellular signals. In liver cells, the similar potentiation between insulin and camp was observed, suggesting that the cross-talk mechanisms are very important to control insulin-like activities in general. From a series of these data, we concluded that IGF bioactivities are modulated by the process of 1) IGFs production, 2) IGFBPs production, 3) interaction between IGFs and IGFBPs, 4) IGF receptor expression, and 5) IGF signal transduction, in response to other hormones or growth factors as well as physiological conditions. This modulation must be required for normal development and growth of mammals. Less

  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Takenaka A et al.: "Nutritional regulation of gene expression of insulin-like growth factor-binding proteins and the acid-labile subunit in various tissues of rats." J. Endocrinal.150. 33-41 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takenaka A et al.: "Nutritional regulation of insulin-like growth factor-I receptor." J. Nutr. Sci. Vit.42. 347-357 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Higashi Y et al.: "Effect of proteins restriction on the messenger ribonucleic acids contents of bone matrix proteins, insulin-like growth factors and insulin-like growth factor binding proteins in femur of ovaricctomized rats." Brit. J. Nutr.75. 811-823 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inaba T et al.: "Effects of growth hormone and insulin-like growth factor I teratments on the nitrogen metabolism and hepatic IGF-I-mRNA expression in postoperative parenterally fed rats." J. Parenteral and Enteral Nutrition. 20. 325-331 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inaba T et al.: "Effects of growth hormone and insulin like growth factor 1 on hepatic IGF-1-mRNA, plasma IGF-1 and nitorgen excretion in gastrectomized rats with liver cirrhosis." Clinical Nutrition. 15. 321-325 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito Y et al.: "Interaction between cAMP-dependent and insulin-dependent signal pathways in tyrosine phosphorylation in primary cultures of hepatocytes." Biochem. J.324. 379-388 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito Y et al.: "Phosphorylation of insulin receptor, insulin receptor substrate 1 (IRS-1) and association of phosphatidylinositol 3-kinase subunit with IRS-1 after meal in vivo in rat liver." J.Endocrinol.154. 267-273 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inaba T et al.: "Insulin-like growth factor 1 has beneficial effects, while growth hormone has limited effects, on postoperative protein metabolism, gut integrity and splenic weight in rats with chronic nild liver injuly." J. Parenteral and Enteral Nutrition. 21. 55-62 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito Y et al.: "Starvation enhanced insulin-dependent tyrosine phosphorylation of the 195 kDa protein in rat intact liver." Biosci. Biotech. Biochem.61. 2122-2124 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Koide T et al.: "Insulin-like growth factor-I potentiates protein synthesis induced by thyrotropin in FRTL-5 cells." Endocrine J.45. 151-163 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Higashi Y et al.: "Effect of protein restriction on the messenger ribonucleic acid contents of insulin-like growth factor-I and insulin-like growth factor binding proteins in liber of ovariectomized rats." Brit. J. Nutr.79. 447-453 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyatake N et al.: "Differential disribution of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding proteins (IGFBPs) in experimental diabetic rat kidney." Nephron. In press.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Uchijima Y et al.: "Dexamethasone induces IGFBP-1 gene transcription as well as stabilizes IGFBP-1 mRNA in primary cultures of rat hepatocytes." Endocrine J.In press.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 高橋 伸一郎: "インスリン様成長因子とは何か." 日本農芸化学会誌. 72. 159-160 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 高橋 伸一郎: "インスリン様成長因子の生理活性の調節." 日本農芸化学会誌. 72. 161-166 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 高橋 伸一郎、 伯野 史彦: "インスリン様成長因子の細胞内シグナル伝達." ホルモンと臨床. 46. 89-104 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 高橋 伸一郎、 伯野 史彦: "インスリン様成長因子をめぐる話題." BIO Clinica. 13. 963-969 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 伯野 史彦、 高橋 伸一郎: "インスリン様成長因子遺伝子を過剰発現あるいは欠損させたらどうなるか" ホルモンと臨床. 印刷中.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takano K, Hizuka N, Takahashi, S-I: "Molecular mechanisms to regulate insulin-like growth factors' activities" Eisevier, Amsterdam, New York, Tokyo, 394 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 高橋 伸一郎、 伯野 史彦: "細胞機能と代謝マップII. IV部細胞間コミュニケーション 24章 増殖因子" 東京化学同人, 14 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takenaka A et al.: "Nutritional regulation of gene experssion of insulin-like growth factor-binding proteins and the acid-labile subunit in various tissues of rats." J.Endocrinol.150. 33-41 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takenaka A et al.: "Nutritional regulation of insulin-like growth factor-1 receptor." J.Nutr.Sci.Vit.42. 347-357 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Higashi Y et al.: "Effect of proteins restriction on the messenger ribonucleic acids contents of bone matrix proteins, insulin-like growth factors and insulin-like growth factor binding proteins in femur of ovarieetomized rats." Brit.J.Nutr.75. 811-823 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inaba T et al.: "Effects of growth hormone and insulin-like growth factor I treatments on the nitrogen metabolism and hepatic IFG-1-mRNA expression in postoperative parenterally fed rats." J.Par.Ent.Nutr.20. 325-331 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inaba T et al.: "Effects of growth hormone and insulin like growth factor I on hepatic IGF-I-mRNA,plasma IGF-I and nitrogen excretion in gastrectomized rats with liver cirrhosis." Clinical Nutrition. 15. 321-325 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito Y et al: "Interaction between cAMP-dependent and insulin-dependent signal pathways in tyrosine phosphorylation in primary cultures of rat hepatocytes." Biochem.J.324. 379-388 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito Y et al: "Phosphorylation of insulin receptor, insulin receptor substrate-1 (IRS-1) and association of phosphatidylinositol 3-kinase subunit with IRS-1 after a meal in vivo in rat liver." J.Endocrinol.154. 267-273 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inaba T et al.: "Insulin-like growth factor 1 has beneficial effects, while growth hormone has limited effects, on postoperative protein metabolism, gut integrity and splenic weight in rats with chronic nild liver injuly." J.Par.Ent.Nutr.21. 55-62 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito Y et al.: "Starvation enhanced insulin-dependent tyrosine phosphorylation of the 195kDa protein in rat intact liver." Biosci.Biotech.Biochem.61. 2122-2124 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koide T et al.: "Insulin-like growth factor-I potentials protein synthesis iniduced by thyrotropin in FRTL-5 cells." Endocrine J.45. 151-163 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Higashi Y et al.: "Effect of protein restriction on the messenger ribonucleic acid contents of insulin-like growth factor-I and insulin-like growth factor binding proteins in liver of ovariectomized rats." Brit.J.Nutr.79. 447-453 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyatake N et al.: "Differential distribution of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding proteins (IGFBPs) in experimental diabetic rat kidney." Nephron. in press.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Uchijima Y et al.: "Dexamethasone induces IGFBP-1 gene transcription as well as stabilizes IGFBP-1 mRNA in primary cultures of rat" Endocrine J.(In press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi S-I: "Mini-review : What are insulin-like growth factors? (Japanese)" Nippon Nougei Kagaku Kaishi. 72. 159-160 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi S-I: "Mini-review : Regulation of insulin-like growth factors' activities (Japanese)" Nippon Nougei Kagaku Kaishi. 72. 161-166 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi S-I,Hakuno F: "Signal transduction of insulin-like growth factors (Japanese)" Clinical Endocrinology. 46. 89-103 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi S-I,Hakuno F: "New insights into regulation of insulin-like growth factors' activities (Japanese)" BIO Clinica. 13. 963-969 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hakuno F,Takahashi S-I: "Animal overexpressing or disrupting insulin-like growth factors genes-Analysis of IGFs and their receptors function using transgenic and knock-out mice- (Japanese)" Clinical Enodcrinology. In press.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takano K,Hizuka N,Takahashi S-I ed: Molecular mechanisms to regulate insulin-like growth factors' activities. Elsevier, Amsterdam, New York, Tokyo., (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi S-I,Hakuno F: Growth factors. In : Cellular Signalling. (Japanese). Tokyo Kagaku Dojin Press., 186-199 (1998)

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

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Published: 1999-12-08  

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