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PPARγ antagonist ameliorates obesity, insulin resistance and atherosclerosis.

Research Project

Project/Area Number 13557092
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Metabolomics
Research Institutionthe University of Tokyo

Principal Investigator

TOBE Kazuyuki  the University of Tokyo, Facully of Medicine, Research Associate, 医学部附属病院, 助手 (30251242)

Co-Investigator(Kenkyū-buntansha) TERAUCHI Yasuo  the University of Tokyo, Facully of Medicine, Research Associate, 医学部附属病院, 助手 (40359609)
YAMAUCHI Toshimasa  the University of Tokyo, Facully of Medicine, medical staff, 医学部附属病院, 医員
KADOWAKI Takashi  the University of Tokyo, Facully of Medicine, Associate Professor, 医学部附属病院, 助教授 (30185889)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2002: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 2001: ¥6,300,000 (Direct Cost: ¥6,300,000)
Keywordsobesity / insulin / resistance / PPARγ / adipocytes / leptin / thiazolidine / adiponectin
Research Abstract

In order to clarify the mechanism of high-fat diet-induced insulin resistance and obesity, we generated PPARγ knockout mice. Hetrozygotes for PPARγ gene were resistant to high fat diet-induced obesity and insulin resistance (Molecula Cell 4: 597, 1999). We also demonstrated that mice fed with high fat diet treated with PPARγ antagonists were resistant to insulin resistance and obesity (Nature Medicine 7: 941, 2001; J, Biol, Chem. 276: 41245, 2001), suggesting that reduced function of PPARγ in adipocytes results in the reduction of adipocyte size and amelioration if systemic insulin resistance (J. Cin.In vest. 108: 1001, 2001).
We also the reduced expression of leptin and adiponectin gene in smaller adipocytes from PPARγ+/-mice and high-fat fed mice treated with PPARγ antagonist. In addition, we demonstrated that heterozygotes for CBP gene disruption are much more resistant to obesity and insulin resistance and diabetes on a high fat diet, providing evidence that increesed energy consump … More tion and insulin sensitivity was due to increase leptin sensitivity and serum adiponectin levels (Nature Genetics 30: 221, 2002).
We also demonstrated that adiponectin reduced triglyceride contents of insulin's target organ by promoting the combustion of lipid stored in liver and skeletal muscle through the activation of AMP kinase and PPARγ ligand (Nature Medicine 8: 1288, 2002; J. Biol. CHem. 278: 2461, 2003). We further demonstrated that improved atherosclerotic lesion was observed in apoE-/-mice which crossed with adiponectin overxpressed transgenic mice(J. Biol. Chem. 278: 2461, 2003).
In order to study the mechanism of insulin resistance, we generated several model mice by gene targeting. So fai, we generated mice deficient in insulin receptor substrate (IRS)-1 (Tamemoto, et al.: Nature 372: 182-186, 1994) PI3 kinase p85 regulatory subunit (Terauchi, et al.: Nature Genetics 21: 230-235, 1999) and PPARγ gene (Kubota, et al.: Mol. Cell 4: 567-609, 1999). These mice enabled us to dissect (1)how insulin resistance and insulin secretory dysfunction lead to the development of diabetes, (2)how defects in each organ such us liver, skeletal muscle, adipose tissue and pancreatic β cells are responsible for the development of diabetes. We also were able to find pathways which compensate for the targeted gene. Although IRS-1 deficient mice were insulin resistant, they remaind normal glucose tolerance, because insulin resistance was compensated by hyperinsulinemia associated with β cell hyperplasia (Yamauchi, et al.: Mol. cell. Biol. 16: 3074-3084, 1996). By crossing IRS-1^<-/-> mice with glucokinase deficient mice with insulin secretory dysfunction, we came to the conclusion that both insulin resistance and insulin secretory dysfunction are necessary for the development of diabetes (Terauchi, et al.: J. Clin. Invest. 99: 861-866, 1997).
We also demonstrated that IRS-1^<-/-> mice were a model for "Syndrome X" because they showed insulin resistance in skeletal muscle, hypertriglycerolemia, lower HDL Chol, hypertension and endothelial dysfunction (Abe, et al.: J. Cin.Invest. 101: 1784-1788, 1998.). We also found a novel insulin receptor substrate, (IRS-2) which compensated IRS-1 and mediated insulin action in IRS-1^<-/-> mice (Tobe, et al.: J. Biol. Chem. 270: 5698-5701, 1995). Currently, we generated IRS-2 deficient mice and demonstrated that these mice developed diabetes due to insulin resistance in liver and β cell growth failure (Kubota, et al.: Diabetes 49: 1880-1889, 2000). We also reported that IRS-2^<-/-> mice developed obesity and fatty liver due to leptin resistance in the hypothrlamus (Tobe, et al.: J. Biol. Chem. 276-38337-38340, 2001). Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (75 results)

All Other

All Publications (75 results)

  • [Publications] Terauchi, Y., et al.: "Impact of genetic background and ablation of IRS-3 on IRS-2 knockout mice."J.Biol.Chem.. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tobe, K., et al.: "Cytoskeletal reorganization induced byinsulin : involvement of Grb2/Ash, Ras and phosphatidylinositol 3-kinase signaling."Genes to Cells. 8. 29-40 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamauchi, T., et al.: "Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis."J.Biol.Chem. 24. 2461-2468 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamauchi, T., et al.: "Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase."Nat Med.. 8. 1288-1295 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kubota, N., et al.: "Disruption of adiponectin causes insulin resistance and neointimal formation."J.Biol.Chem.. 19. 25863-25866 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamauchi, T., et al.: "Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice."Nat Genet.. 30. 221-226 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Imai, Y., et al.: "Resistance to neointimal hyperplasia and fatty streak formation in mice with adrenomedullin overexpression."Arterioscler Thromb Vasc Biol.. 22. 1310-1315 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kadowaki, T., et al.: "The role of PPARgamma in high-fat diet-induced obesity and insulin resistance."J.Diabetes Complications. 16. 41-45 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hara, K., et al.: "A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes."Diabetologia. 45. 740-743 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hara, K., et al.: "Maturity-onset diabetes of the young resulting from a novel mutation in the HNF- 4alpha gene."Intern Med.. 41. 848-852 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Eto, K., et al.: "Phosphatidylinositol 3-kinase suppresses glucose-stimulated insulin secretion by affecting post-cytosolic [Ca(2+)] elevation signals."Diabetes. 51. 87-97 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mori, Y., et al.: "Genome-wide search for type 2 diabetes susceptibility genes in Japanese affected sibpairs. Autosomal scan supplemented with markers for 12 transcription factor genes and adiponectin gene."Diabetes. 51. 1247-1255 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hara K., et al.: "Genetic variation in the gene encoding adiponectin is associated with increased risk of type 2 diabetes in the Japanese population."Diabetes. 51. 536-540 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akune, T., et al.: "Insulin receptor substrate-2 maintains predominance of anabolic function over catabolic function of osteoblasts."J.Cell Biol.. 159. 147-156 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shindo, T., et al.: "Kruppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling."Nature Medicine. 8. 856-863 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hara, K., et al.: "Role of PPARγ as a thrifty gene in high-fat diet-induced adipocyte hypertrophy and insulin resistance."Brit.J.Nutr. 84. 235-239 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuji, Y., et al.: "Distinct subcellular localization and IRS family proteins associating P13-kinase activity following insulin stimulation and its functional implications in primary mice adipocytes."Diabetes. 50. 1455-1463 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miki, H., et al.: "Essential role of IRS-1 and IRS-2 in adipocyte differentiation."Mol.Cell.Biol.. 21. 2521-2531 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamauchi, T., et al.: "The mechanisms by which both heterozygous PPARγ deficiency and PPARγ agonist improve insulin resistance."J.Biol.Chem.. 276. 41245-41254 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamauchi, T., et al.: "Inhibition of RXR and PPARgamma ameliorates diet-induced obesity and type 2 diabetes."J.Clin.Invest.. 108. 1001-1013 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chen, W.S., et al.: "Growth retardation and increased apoptosis in mice with homozygous disruption of the akt1 gene."Genes Dev.. 15. 2203-2208 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamauchi, T., et al.: "Replenishment of the fat-derived hormone adiponectin reverses insulin resistance in lipoatrophic diabetes and type 2 diabetes."Nature Medicine. 7. 941-946 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tobe, K., et al.: "Increased Expression of SREBP-1 gene in IRS-2(-/-) mice liver."J.Biol.Chem.. 276. 38337-38340 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Terauchi Y, et al.: "Impact of genetic background and ablation of IRS-3 on IRS-2 knockout mice."J.Biol.Chem.. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tobe, K., et al.: "Cytoskeletal reorganization induced byinsulin: involvement of Grb2/Ash, Ras and phosphatidylinositol 3-kinase signa1ing."Genes to Cells. 8. 29-40 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamauchi, T., et al.: "Globular adiponection protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis."J. Biol. Chem.. 278. 2461-2468 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamauchi, T., et al.: "Adiponectin stimulates glucose utilization and fatty-acid oxidation by activ aling AMP-activated protein kinase."Nat. Med.. 8. 1288-1295 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kubota, N., et al.: "Disruption of adiponectin causes insulin resistance and neointimal formation."J. Biol. Chem.. 277. 25863-25866 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Imai Y, et al.: "Resistance to neointimal hyperplasia and fatty streak formation in mice with adrenomedullin overexpression."Arterioscler Thromb. Vasc. Biol.. 22. 1310-1315 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kadowaki, T., et al.: "The role of PPARgamma in high-fat diet-induced obesity and insulin resistance."J. Diabetes Complications.. 16. 41-45 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hara K, et al.: "A genetic variation in the PGC-1 gene could confer insulin resistance and usceptibility to Type II diabetes."Diabetologia. 45. 740-743 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hara, K., et al.: "Maturity-onset diabetes of the young resulting from a novel mutation in the HNF-4alpha gene."Intern Med.. 41. 848-852 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Eto, K., et al.: "Phospliatidylinositol 3-kinase suppresses glucose-stimulated insulin secretion by affecting post-cytosolic Ca(2+) elevation signals."Diabetes. 51. 87-97 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mori, Y., et al.: "Genome-wide search for type 2 diabetes susceptibility genes in Japanese affected sibpairs. Autosomal scan supplemented with markers for 12 transcription factor genes and adiponectin gene."Diabetes. 51. 87-97 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hara, K., et al.: "Genetic variation in the gene encoding adiponectin is associated with increasedrisk of type 2 diabetes in the Japanese population."Diabetes. 51. 536-540 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akune T, et al.: "Insulin receptor substrate-2 maintains predominance of anabofic function over catabolic function of osteoblasts."J. Cell Biol.. 159. 147-156 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shindo T, et al.: "Kruppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling."Nature Medicine. 8. 856-863 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hara, K., et al.: "Role of PPARγ as a thrifty gene in high-fat diet-induced adipocyte hypertrophy and insulin resistance."Brit. J. Nutr. 84. 235-239 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuji, Y., et al.: "Distinct subcellular localization and IRS family proteins associating PI3-kinase activity following insulin stimulation and its functional implications in primary mice adipocytes."Dinbetes. 50. 1455-1463 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miki, H., et al.: "Essential role of IRS-1 and IRS-2 in adipocyte differentiation."Mol.Cell.Biol. 21. 2521-2531 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamauchi, T, et al.: "The mechanisms by which both heterozygous PPARγ deficiency and PPARγ agonist improve insulin resistance."J.Biol. Chem.. 276. 41245-41254 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamauchi, T., et al.: "Inhibilion of RXR and PPARgamma ameliorates diet-induced obesity and type 2 diabetes."J.Clin. Invest.. 108. 1001-1013 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chen, et al.: "Growth retardation and increased apoptosis in mice with homozygous disruplion of the akt1 gene."Genes Dev.. 15. 2203-2208 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamauchi, T, et al.: "Replenishment of the fat-derived hormone adiponectin reverses insulin resistance in lipoatrophic diabetes and type 2 diabetes."Nature Medicine. 7. 941-946 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tobe, K., et al.: "Increased Expression of SREBP-1 gene in IRS-2(-/-) mice liver."J.Biol.Chem.. 276. 38337-38340 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Terauchi, Y., et al.: "Impact of genetic background and ablation of IRS-3 on IRS-2 knockout mice"J.Biol.Chem.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tobe, K., et al.: "Cytoskeletal reorganization induced byinsulin : involvement of Grb2/Ash, Ras and phosphatidylinositol 3-kinase signaling"Genes to Cells. 8. 29-40 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamauchi, T., et al.: "Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis"J.Biol.Chem.. 278. 2461-2468 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamauchi, T., et al.: "Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase"Nat.Med.. 8. 1288-1295 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kubota, N., et al.: "Disruption of adiponectin causes insulin resistance and neointimal formation"J.Biol.Chem.. 277. 25863-25866 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Imai, Y., et al.: "Resistance to neointimal hyperplasia and fatty streak formation in mice with adrenomedullin overexpression"Arterioscler Thromb Vasc Biol.. 22. 1310-1315 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kadowaki, T., et al.: "The role of PPARgamma in high-fat diet-induced obesity and insulin resistance"J. Diabetes Complications. 16. 41-45 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hara, K., et al.: "A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes"Diabetologia. 45. 740-743 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hara, K., et al.: "Maturity-onset diabetes of the young resulting from a novel mutation in the HNF-4alpha gene"Intern Med.. 41. 848-852 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Eto, K., et al.: "Phosphatidylinositol 3-kinase suppresses glucose-stimulated insulin secretion by affecting post-cytosolic [Ca(2+)] elevation signals"Diabetes. 51. 87-97 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mori, Y., et al.: "Genome-wide search for type 2 diabetes susceptibility genes in Japanese affected sibpairs. Autosomal scan supplemented with markers for 12 transcription factor genes and adiponectin gene"Diabetes. 51. 1247-1255 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hara, K., et al.: "Genetic variation in the gene encoding adiponectin is associated with increased risk of type 2 diabetes in the Japanese population"Diabetes. 51. 536-540 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akune, T., et al.: "Insulin receptor substrate-2 maintains predominance of anabolic function over catabolic function of osteoblasts"J.Cell Biol.. 159. 147-156 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shindo, T., et al.: "Kruppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling"Nature Medicine. 8. 856-863 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hara, K., et al.: "Role of PPARγ as a thrifty gene in high-fat diet-induced adipocyte hypertrophy and insulin resistance"Brit.J.Nutr. 84. 235-239 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsuji, Y., et al.: "Distinct subcellular localization and IRS family proteins associating PI3-kinase activity following insulin stimulation and its functional implications in primary mice adipocytes"Diabetes. 50. 1455-1463 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miki, H., et al.: "Essential role of IRS-1 and IRS-2 in adipocyte differentiation"Mol.Cell.Biol.. 21. 2521-2531 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamauchi, T., et al.: "The mechanisms by which both heterozygous PPARγ deficiency and PPARγ agonist improve insulin resistance"J.Biol.Chem.. 276. 41245-41254 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamauchi, T., et al.: "Inhibition of RXR and PPARgamma ameliorates diet-induced obesity and type 2 diabetes"J.Clin.Invest.. 108. 1001-1013 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Chen, W.S., et al.: "Growth retardation and increased apoptosis in mice with homozygous disruption of the akt1 gene"Genes Dev.. 15. 2203-2208 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamauchi, T., et al.: "Replenishment of the fat-derived hormone adiponectin reverses insulin resistance in lipoatrophic diabetes and type 2 diabetes"Nature Medicine. 7. 941-946 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tobe, K., et al.: "Increased Expression of SREBP-1 gene in IRS-2(-/-) mice liver"J.Biol.Chem.. 276. 38337-38340 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hara, K., et al.: "Genetic variation in the gene encoding adiponectin is associated with increased risk of type 2 diabetes in the Japanese population"Diabetes. 51. 536-540 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tobe, K., et al.: "Increased Expression of SREBP-1 gene in IRS-2(-/-)mice liver"J. Biol. Chem.. 276. 38337-38340 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamauchi.T., et al.: "Replenishment of the fat-derived hormone adiponectin reverses insulin resistance in lipoatrophic diabetes and type 2 diabetes"Nature Medicine. 7. 941-946 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamauchi.T., et al.: "The central role of PPARγ in the regulation of insulin sensitivity"J. Clin. Invest.. 108. 1001-1013 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamauchi.T., et al.: "The mechanisms by which both heterozygous PPARγ deficiency and PPARγ agonist improve insulin resistance"J. Biol. Chem.. 276. 41245-41254 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miki, H., et al.: "Essential role of IRS-1 and IRS-2 in adipocyte differentiation"Mol. Cell. Biol.. 21. 2521-2531 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsuji, Y., et al.: "Distinct subcellular localization and IRS family proteins associating PI3-kinase activity following insulin stimulation and its functional implications in primary mice adipocytes"Diabetes. 50. 1455-1463 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kubota, N., et al.: "Disruption of insulin receptor substrate-2 causes type 2 diabetes due to liver insulin resistance and lack of compemsatory β cell hyperplasia"Diabetes. 49. 1880-1889 (2000)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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