@article{6fe1182cb70e4a2eb8a1def2d79679cf,
title = "Cloning of adiponectin receptors that mediate antidiabetic metabolic effects",
abstract = "Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30) is a hormone secreted by adipocytes that acts as an antidiabetics 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-α. 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-α ligand activities, as well as fatty-acid oxidation and glucose uptake by adiponectin.",
author = "Toshimasa Yamauchi and Junji Kamon and Yusuke Ito and Atsushi Tsuchida and Takehiko Yokomizo and Shunbun Kita and Takuya Sugiyama and Makoto Miyagishi and Kazuo Hara and Masaki Tsunoda and Koji Murakami and Toshiaki Ohteki and Shoko Uchida and Sato Takekawa and Hironori Waki and Tsuno, {Nelson H.} and Yoichi Shibata and Yasuo Terauchi and Philippe Froguel and Kazuyuki Tobe and Shigeo Koyasu and Kazunari Taira and Toshio Kitamura and Takao Shimizu and Ryozo Nagai and Takashi Kadowaki",
note = "Funding Information: Acknowledgements We are grateful to members of our laboratory for discussions and for critical reading of the manuscript. We are also grateful to J. Gannon and T. Hunt for discussions as well as human CDK antibodies and p13suc1 beads. We thank L. Drury, K. Labib, J. Li, G. Perkins and S. Reed for yeast strains. We also thank N. O{\textquoteright}Reilly and the Peptide Synthesis Facility at the London Research Institute. This work was supported by Cancer Research UK and the Human Frontier Science Program Organization. S.M. is supported by JSPS postdoctoral Fellowships for Research Abroad. Funding Information: Acknowledgements We thank S. van Eeden for technical assistance and H. Rothnie, K. Smith and E. Schultz for comments on the manuscript. The Novartis Research Foundation and Alberta Ingenuity Grant are acknowledged for financial support. Funding Information: Acknowledgements We are grateful to K. Kirii, A. Itoh, A. Okano, T. Nagano and S. Nakamura for their technical assistance. This work was supported by a Grant-in-Aid for Creative Scientific Research from the Japan Society for the Promotion of Science (to T.K.), and by Health Science Research Grants (Research on Human Genome and Gene Therapy) from the Ministry of Health and Welfare (to T.K.).",
year = "2003",
month = jun,
day = "12",
doi = "10.1038/nature01705",
language = "英語",
volume = "423",
pages = "762--769",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Research",
number = "6941",
}