Structure and function analysis of adiponectin receptors toward development of novel antidiabetic agents promoting healthy longevity
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- Okada-Iwabu Miki
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Laboratory for Advanced Research on Pathophysiology of Metabolic Diseases, The University of Tokyo, Tokyo, Japan
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- Iwabu Masato
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Integrated Molecular Science on Metabolic Diseases, 22nd Century Medical and Research Center, The University of Tokyo, Tokyo, Japan PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan
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- Yamauchi Toshimasa
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan AMED-CREST, Japan Agency for Medical Research and Development, Tokyo, Japan
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- Kadowaki Takashi
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Prevention of Diabetes and Life-style Related Diseases, The University of Tokyo, Tokyo, Japan Department of Metabolism and Nutrition, Teikyo University Mizonokuchi Hospital, Kawasaki, Kanagawa, Japan
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Abstract
<p>Plasma adiponectin levels and expression of its receptors, AdipoRs are decreased in obesity, which cause insulin resistance and diabetes. AdipoR-deficient mice exhibit insulin resistance and impaired glucose tolerance. Moreover, newly identified AdipoR agonists not only improve insulin resistance but prolong lifespan shortened by obesity via AdipoR. Furthermore, efforts to promote structure-based drug discovery research at our laboratory have led to the first ever successful crystallization of AdipoR as well as to clarification of their structures. Structural analysis of AdipoRs as key molecules in lifestyle-related diseases is thus expected to lead not only to the acceleration of structure-based drug discovery but to the elucidation of novel aspects of the AdipoR structures and functions in the years to come. Finally, with the development of novel AdipoR-targeted antidiabetic agents also capable of prolonging lifespan, the attainment of healthy longevity may finally be brought within reach.</p>
Journal
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- Endocrine Journal
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Endocrine Journal 65 (10), 971-977, 2018
The Japan Endocrine Society