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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
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥9,800,000 (Direct Cost: ¥9,800,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥5,900,000 (Direct Cost: ¥5,900,000)
Keywordsinsulin resistance / PPARg / knockout mouse / PPARγ / チアゾリジンジオン
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.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Related Report
      2000 Annual Research Report
  • [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)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kubota,N. et al: "PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy an resistance"Mol.Cell. 4(4). 597-609 (1999)

    • Related Report
      2000 Annual Research Report
  • [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)

    • Related Report
      2000 Annual Research Report
  • [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)

    • Related Report
      2000 Annual Research Report
  • [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)

    • Related Report
      2000 Annual Research Report
  • [Publications] Terauchi,Y. 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)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kubota,N. et al.: "PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance"Mol,Cell. 4(4). 597-609 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroyuki Tamemoto et al.: "The role of peroxysome proliferator activated receptor g(PPARg) in the development of mouse placenta"Placenta. 20. A4 (1999)

    • Related Report
      1999 Annual Research Report
  • [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). 1237-1244 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroyuki Tamemoto et al.: "Insulin stimulates phosphorylation and translocation of a transcription factor FKHR"Diabetes. 48 supple 1. A65 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 為本浩至 他: "インスリン刺激による転写因子FKHRの燐酸化と細胞内局在の変化"糖尿病. 42 supple 1. S-35 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Lu D,Tamemoto H,Shibata H,Saito I.Takeuchi T: "Regulatable production of insulin from primary-cultured hepatocytes:insulin production is up-regulated by glucagon and cAMP and down-regulated by insulin." Gene Ther. 5巻7号. 888-95 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamauchi T,Ueki K,Tobe K,Tamemoto H,et al.: "Growth hormone-induced tyrosine phosphorylation of EGF receptor as an essential element leading to MAP kinase actvation and gene expression." Endocr J. 45巻補遺. S27-31 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Abe H,Yamada N,Kamata K,Kuwaki T,et al.: "Hypertension,hypertriglyceridemia,and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1." J Clin Invest. 101巻8号. 1784-8 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Okuno A,Tamemoto H,Tobe K,Ueki K,et al.: "Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats." J Clin Invest. 101巻6号. 1354-61 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tamemoto H,Izumi T,Kaburagi Y,Terauchi Y,et al.: "IRS-1ノックアウトマウス" 日本臨床 56巻補遺3号, 738-45 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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