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2000 Fiscal Year Final Research Report Summary

SEARCH FOR NEW TARGET GENE FOR INSULIN SENSITIZER

Research Project

Project/Area Number 10557103
Research Category

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

Allocation TypeSingle-year Grants
Section展開研究
Research Field Metabolomics
Research InstitutionINSTITUTE FOR MOLECULAR AND CELLULAR RBGULTION (I.M.C.R.), GUNMA UNIVERSITY

Principal Investigator

TAMEMOTO Hiroyuki  I.M.C.R.GUNMA UNIV, ERSITY Department of Molecular Medicine Assistant Professor, 生体調節研究所, 講師 (90292630)

Co-Investigator(Kenkyū-buntansha) IZUMI Tetsuro  I.M.C.R.GUNMA UNIV, ERSITY Department of Molecular Medicine Professor, 生体調節研究所, 教授 (00212952)
Project Period (FY) 1998 – 2000
Keywordsinsulin resistance / PPARg / knockout mouse
Research Abstract

We made knockout mice of the peroxysomal proliferator activated receptor (PPAR γ) which is the receptor for the insulin sensitizer, thiazolidinedione. The homozygous fetus died in the uterus and we could not make a library from homozygous adult mice. The fibroblasts taken from the homozygous fetus were refractory to induction of the development to the adipocyte. The heterozygous mice were apparently healthy and were relatively resistant to obesity when fed high fat diet as compared with the wild type. They also showed better insulin sensitivity after high fat diet (Kubota N.et al. 1999) The homozygous fetus died between 10 to 11 days after coitus and showed no gross anatomical abnormality. The placenta of the homozygous fetus was impaired in the development of its labyrinth zone. We made a negative dominant construct of PPARγ (Pro427Leu) and subcloned this cDNA in a vector that express the gene under control of Cre-loxP system. We are planning to express the negative dominant PPAR in a tissue specific manner.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Ueki K,Yamauchi T,Tamemoto H. et al.: "Restored insulin-sensitivity in IRS-1-deficient mice treated by adenovirus-mediated gene therapy."J Clin Invest.. 105(10):. 1437-45 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Terauchi Y,Kubota N,Tamemoto H. et al.: "Insulin effect during embryogenesis determines fetal growth : a possible molecular link between birth weight and susceptibility to type 2 diabetes."Diabetes.. 49(1). 82-86 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kubota,N. et al: "PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy an resistance"Mol.Cell. 4(4). 597-609 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroyuki Tamemoto et al: "The role of peroxysome proliferator activated receptor g(PPARg) in the development of mouse placenta"Placenta. 20. A-4 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirayama,I. et al: "Insulin receptor-related receptor is expressed in pancreatic beta-cells and stimulates tyrosine phosphorylation of insulin receptor substrate-1 and -2"Diabetes. 48(6). 1237-44 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 為本浩至,泉哲郎,竹内利行: "分子糖尿病学の進歩-基礎から臨床まで-2000Aktキナーゼによる転写因子FKHRの制御"金原出版. (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirayama, I., Tamemoto, H., Yokota, H., Kubo, S.K., Wang, J., Kuwano, H., Nagamachi, Y., Takeuchi, T., Izumi, T.: "Insulin receptor-related receptor is expressed in pancreatic beta-cells and stimulates tyrosine phosphorylation of insulin receptor substrate-1 and -2."Diabetes. 48(6). 1237-1244 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kubota, N., Terauchi, Y., Miki, H., Tamemoto, H., et al.: "PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance."Mol Cell. 4(4). 597-609 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ueki K, Yamauchi T, Tamemoto H, et al.: "Restored insulin-sensitivity in IRS-1-deficient mice treated by adenovirus-mediated gene therapy."J Clin Invest.. 105(10). 1437-45 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Terauchi Y, Kubota N, Tamemoto H.et al.: "Insulin effect during embryogenesis determines fetal growth : a possible molecular link between birth weight and susceptibility to type 2 diabetes"Diabetes.. 49(1). 82-86 (2000)

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

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Published: 2002-03-26  

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