Cloning of adiponectin receptors that mediate antidiabetic metabolic effects (original) (raw)

Nature volume 423, pages 762–769 (2003)Cite this article

A Corrigendum to this article was published on 28 October 2004

Abstract

Corrigendum (2004)

Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30)1,2,3,4 is a hormone secreted by adipocytes that acts as an antidiabetic5,6,7,8,9,10,11,12 and anti-atherogenic8,12,13 adipokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance and type 2 diabetes2. Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice5,6,7. Conversely, adiponectin-deficient mice exhibit insulin resistance and diabetes8,9. This insulin-sensitizing effect of adiponectin seems to be mediated by an increase in fatty-acid oxidation through activation of AMP kinase10,11 and PPAR-α5,6,12. Here we report the cloning of complementary DNAs encoding adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) by expression cloning14,15,16. 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 receptors17,18,19. Expression of AdipoR1/R2 or suppression of AdipoR1/R2 expression by small-interfering RNA20 supports our conclusion that they serve as receptors for globular and full-length adiponectin, and that they mediate increased AMP kinase10,11 and PPAR-α ligand activities12, as well as fatty-acid oxidation and glucose uptake by adiponectin.

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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.).

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Author notes

  1. Toshimasa Yamauchi, Junji Kamon and Philippe Froguel: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, 113-8655, Tokyo, Japan
    Toshimasa Yamauchi, Junji Kamon, Yusuke Ito, Atsushi Tsuchida, Shunbun Kita, Kazuo Hara, Shoko Uchida, Sato Takekawa, Hironori Waki, Yasuo Terauchi, Kazuyuki Tobe, Ryozo Nagai & Takashi Kadowaki
  2. CREST of Japan Science and Technology Corporation, 332-0012, Japan
    Toshimasa Yamauchi, Kazuo Hara, Toshiaki Ohteki, Hironori Waki, Yasuo Terauchi, Kazuyuki Tobe, Shigeo Koyasu & Takashi Kadowaki
  3. Biological Research Laboratories, Nissan Chemical Industries, Saitama, 349-0294, Japan
    Junji Kamon
  4. Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Tokyo, Tokyo, 113-0033
    Takehiko Yokomizo & Takao Shimizu
  5. CREST and PRESTO of JST, Japan
    Takehiko Yokomizo & Takao Shimizu
  6. Division of Hematopoietic Factors, Institute of Medical Science, University of Tokyo, 108-8639, Tokyo, Japan
    Takuya Sugiyama & Toshio Kitamura
  7. Department of Chemistry and Biotechnology, School of Engineering, University of Tokyo, 113-8656, Tokyo, Japan
    Makoto Miyagishi & Kazunari Taira
  8. Gene Function Research Center, National Institute of AIST, Tsukuba, 305-8562, Japan
    Makoto Miyagishi & Kazunari Taira
  9. Central Research Laboratories, Kyorin Pharmaceutical, Tochigi, 329-0114, Japan
    Masaki Tsunoda & Koji Murakami
  10. Department of Microbiology and Immunology, Keio University School of Medicine, 160-8582, Tokyo, Japan
    Toshiaki Ohteki & Shigeo Koyasu
  11. Department of Transfusion Medicine, Graduate School of Medicine, University of Tokyo, 113-8655, Tokyo, Japan
    Nelson H. Tsuno & Yoichi Shibata
  12. Institute of Biology-CNRS, Pasteur Institute of Lille, UPRES, A8090, 59000, Lille, France
    Philippe Froguel

Authors

  1. Toshimasa Yamauchi
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  2. Junji Kamon
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  3. Yusuke Ito
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  4. Atsushi Tsuchida
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  5. Takehiko Yokomizo
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  6. Shunbun Kita
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  7. Takuya Sugiyama
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  8. Makoto Miyagishi
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  9. Kazuo Hara
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  10. Masaki Tsunoda
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  11. Koji Murakami
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  12. Toshiaki Ohteki
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  13. Shoko Uchida
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  14. Sato Takekawa
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  15. Hironori Waki
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  16. Nelson H. Tsuno
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  17. Yoichi Shibata
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  18. Yasuo Terauchi
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  19. Philippe Froguel
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  20. Kazuyuki Tobe
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  21. Shigeo Koyasu
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  22. Kazunari Taira
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  23. Toshio Kitamura
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  24. Takao Shimizu
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  25. Ryozo Nagai
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  26. Takashi Kadowaki
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Correspondence toTakashi Kadowaki.

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Yamauchi, T., Kamon, J., Ito, Y. et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects.Nature 423, 762–769 (2003). https://doi.org/10.1038/nature01705

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