| Project/Area Number |
14207045
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | the University of Tokyo |
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Principal Investigator |
KADOWAKI Takashi the University of Tokyo, faculty of Medicine, Professor, 医学部附属病院, 教授 (30185889)
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| Co-Investigator(Kenkyū-buntansha) |
KUBOTA Naoto the University of Tokyo, faculty of Medicine, Medical Staff, 医学部附属病院, 医員
TOBE Kazuyuki the University of Tokyo, faculty of Medicine, Lecturer, 医学部附属病院, 講師 (30251242)
YAMAUCHI Toshimasa the University of Tokyo, faculty of Medicine, Research Associate, 医学部附属病院, 助手 (40372370)
TERAUCHI Yasuo the University of Tokyo, faculty of Medicine, Research Associate, 医学部附属病院, 助手 (40359609)
HARA Kazuo the University of Tokyo, faculty of Medicine, Visiting Medical Staff, 医学部附属病院, 科学技術振興特任教員(常勤形態) (50359600)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥50,310,000 (Direct Cost: ¥38,700,000、Indirect Cost: ¥11,610,000)
Fiscal Year 2003: ¥24,310,000 (Direct Cost: ¥18,700,000、Indirect Cost: ¥5,610,000)
Fiscal Year 2002: ¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
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| Keywords | adiponectin receptors / obesity / diabetes / adiponectin resistance / fatty acid oxidation / glucose uptake / nuclear receptors / AMP kinase / アディポネクチン / 脂質代謝異常 / インスリン抵抗性 / PPARγ / 動脈硬化 / レプチン |
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| Research Abstract |
Obesity-linked diseases such as diabetes and cardiovascular disease are sharply increasing in developed and developing countries. Heterozygous PPARg or CBP knockout mice were protected from high-fat diet induced obesity and insulin resistance (Mol.Cell 4:597, 1999; Nature Genetics 30:221, 2002). We then carried out systematic gene profiling analysis of these mice and found that adiponectin/Acrp30 was overexpressed. Functional analyses including generation of adiponectin transgenic or knockout mice have revealed that adiponectin serves as an insulin sensitizing adipokine (Nature Medicine 7:941, 2001). In fact, obesity-linked down regulation of adiponectin was a mechanism whereby obesity can cause insulin resistance and diabetes. We further studied the mechanism of adiponectin action and found that adiponectin can activate AMP kinase pathway and PPARa pathway, leading to fat combustion and amelioration of insulin resistance (Nature Medicine 8:1288, 2002). Recently, we have cloned adiponectin receptors in the skeletal muscle (AdipoR1) and liver (AdipoR2), which appear to comprise a novel cell surface receptor family (Nature 423:762, 2003). The expression of AdipoR1/R2 appears to be regulated by several physiological and pathophysiological states such as, fasting/refeeding and hyperinsulinemia, and correlated with adiponectin sensitivity (J.Biol.Chem. published on line on Apr 29, 2004). Adiponectin receptor agonists and adiponectin sensitizers should serve as versatile treatment strategies for obesity linked diseases such as diabetes.
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