Cloning of adiponectin receptors that mediate antidiabetic metabolic effects |
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Authors: | Yamauchi Toshimasa Kamon Junji Ito Yusuke Tsuchida Atsushi Yokomizo Takehiko Kita Shunbun Sugiyama Takuya Miyagishi Makoto Hara Kazuo Tsunoda Masaki Murakami Koji Ohteki Toshiaki Uchida Shoko Takekawa Sato Waki Hironori Tsuno Nelson H Shibata Yoichi Terauchi Yasuo Froguel Philippe Tobe Kazuyuki Koyasu Shigeo Taira Kazunari Kitamura Toshio Shimizu Takao Nagai Ryozo Kadowaki Takashi |
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Affiliation: | Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan. |
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Abstract: | Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30) is a hormone secreted by adipocytes that acts as an antidiabetic and anti-atherogenic adipokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance and type 2 diabetes. Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice. Conversely, adiponectin-deficient mice exhibit insulin resistance and diabetes. This insulin-sensitizing effect of adiponectin seems to be mediated by an increase in fatty-acid oxidation through activation of AMP kinase and PPAR-alpha. Here we report the cloning of complementary DNAs encoding adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) by expression cloning. 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. Expression of AdipoR1/R2 or suppression of AdipoR1/R2 expression by small-interfering RNA supports our conclusion that they serve as receptors for globular and full-length adiponectin, and that they mediate increased AMP kinase and PPAR-alpha ligand activities, as well as fatty-acid oxidation and glucose uptake by adiponectin. |
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