5 :: KDA, Korean Diabetes Association ::
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Subject    :    [2015 Oct;39(5)] Perspective of Small-Molecule AdipoR Agonist for Type 2 Diabetes and Short Life in Obesity
Writer KDA
Date 2015-12-08 10:13:53 Hit 6,436
Diabetes Metab J. 2015 Oct;39(5):363-372. English. Published online Oct 22, 2015.  http://dx.doi.org/10.4093/dmj.2015.39.5.363 
Copyright © 2015 Korean Diabetes Association
   
Perspective of Small-Molecule AdipoR Agonist for Type 2 Diabetes and Short Life in Obesity
Miki Okada-Iwabu,1 Masato Iwabu,1,2 Kohjiro Ueki,3,4 Toshimasa Yamauchi,1,5 and Takashi Kadowaki1
1Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
2PRESTO, Japan Science and Technology Agency, Kawaguchi, Japan.
3Department of Molecular Sciences on Diabetes, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
4Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
5CREST, Japan Science and Technology Agency, Kawaguchi, Japan.
Corresponding author: Takashi Kadowaki. Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Email: kadowaki-3im@h.u-tokyo.ac.jp Corresponding author: Toshimasa Yamauchi. Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.Email: tyamau-tky@umin.net Corresponding author: Kohjiro Ueki. Department of Molecular Sciences on Diabetes, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.Email: ueki-tky@umin.net 
 
 

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

 
Abstract

Obesity associated with unhealthy diet and lack of exercise is shown to contribute to the onset and/or aggravation of the metabolic syndrome and diabetes, thus placing affected individuals at increased risk of cardiovascular disease and cancer. Plasma adiponectin levels are decreased in obesity, which causes insulin resistance and diabetes. Therefore, we identified adiponectin receptors (AdipoRs) as the therapeutic target. It was suggested that, similarly to caloric restriction and exercise, activation of the AdipoRs may have the potential not only to improve lifestyle-related diseases but to contribute to prolonged the shortened lifespan on a high caloric unhealthy diet. To this end, we have identified "AdipoRon" as an adiponectin receptor agonist. Indeed, AdipoRon ameliorated diabetes associated with obesity as well as to increase exercise endurance, thus prolonging shortened lifespan of obese mice fed on a high fat diet. Additionally, we have recently determined the crystal structures of the human AdipoRs. The seven-transmembrane helices of AdipoRs are structurally distinct from those of G-protein coupled receptors. It is expected that these findings will contribute not only to the elucidation of the AdipoR-related signal transduction but to the development and optimization of AdipoR-targeted therapeutics for obesity-related diseases such as diabetes.

   

Keywords: Adiponectin, AdipoR, Agonist, Crystal structure, Diabetes mellitus, Obesity.

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