Cloning of adiponectin receptors that mediate antidiabetic metabolic effects
Cloning of adiponectin receptors that mediate antidiabetic metabolic effects
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DOI：
10.1038/nature01705
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发表时间：
2003-06-12
期刊：
影响因子：
64.8
通讯作者：
Kadowaki, T
中科院分区：
文献类型：
--
作者：
Yamauchi, T;Kamon, J;Kadowaki, T
脂联素（也称为30-kDa脂肪细胞补体相关蛋白; Acrp 30）（1-4）是一种由脂肪细胞分泌的激素，作为抗糖尿病（5-12）和抗动脉粥样硬化（8，12，13）脂肪因子。脂联素在血液中的水平下降的条件下肥胖，胰岛素抵抗和2型糖尿病（2）.脂联素的给药可引起降糖作用并改善小鼠的胰岛素抵抗（5-7）。相反，脂联素缺乏的小鼠表现出胰岛素抵抗和糖尿病（8，9）。脂联素的这种胰岛素增敏作用似乎是通过AMP激酶（10，11）和PPAR-alpha（5，6，12）的活化而增加脂肪酸氧化介导的。在此，我们报道了通过表达克隆来克隆编码脂联素受体1和2（AdipoR 1和AdipoR 2）的互补DNA（14-16）。AdipoR 1在骨骼肌中大量表达，而AdipoR 2主要在肝脏中表达。预计这两种脂联素受体含有7个跨膜结构域，但在结构和功能上与G蛋白偶联受体不同（17-19）。AdipoR 1/R2的表达或小干扰RNA对AdipoR 1/R2表达的抑制20支持了我们的结论，即它们作为球状和全长脂联素的受体，并且它们介导AMP激酶（10，11）和PPAR-alpha配体活性增加（12），以及脂联素对脂肪酸的氧化和葡萄糖的摄取。
Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30)(1-4) is a hormone secreted by adipocytes that acts as an antidiabetic(5-12) and anti-atherogenic(8,12,13) adipokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance and type 2 diabetes(2). Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice(5-7). Conversely, adiponectin-deficient mice exhibit insulin resistance and diabetes(8,9). This insulin-sensitizing effect of adiponectin seems to be mediated by an increase in fatty-acid oxidation through activation of AMP kinase(10,11) and PPAR-alpha(5,6,12). Here we report the cloning of complementary DNAs encoding adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) by expression cloning(14-16). AdipoR1 is abundantly expressed in skeletal muscle, whereas AdipoR2 is predominantly expressed in the liver. These two adiponectin receptors are predicted to contain seven transmembrane domains, but to be structurally and functionally distinct from G-protein-coupled receptors(17-19). Expression of AdipoR1/R2 or suppression of AdipoR1/R2 expression by small-interfering RNA 20 supports our conclusion that they serve as receptors for globular and full-length adiponectin, and that they mediate increased AMP kinase(10,11) and PPAR-alpha ligand activities(12), as well as fatty-acid oxidation and glucose uptake by adiponectin.