Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Nov 28;503(7477):493-9.
doi: 10.1038/nature12656. Epub 2013 Oct 30.

A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity

Miki Okada-Iwabu  1 , Toshimasa Yamauchi, Masato Iwabu, Teruki Honma, Ken-ichi Hamagami, Koichi Matsuda, Mamiko Yamaguchi, Hiroaki Tanabe, Tomomi Kimura-Someya, Mikako Shirouzu, Hitomi Ogata, Kumpei Tokuyama, Kohjiro Ueki, Tetsuo Nagano, Akiko Tanaka, Shigeyuki Yokoyama, Takashi Kadowaki
Affiliations

A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity

Miki Okada-Iwabu et al. Nature. .

Abstract

Adiponectin secreted from adipocytes binds to adiponectin receptors AdipoR1 and AdipoR2, and exerts antidiabetic effects via activation of AMPK and PPAR-α pathways, respectively. Levels of adiponectin in plasma are reduced in obesity, which causes insulin resistance and type 2 diabetes. Thus, orally active small molecules that bind to and activate AdipoR1 and AdipoR2 could ameliorate obesity-related diseases such as type 2 diabetes. Here we report the identification of orally active synthetic small-molecule AdipoR agonists. One of these compounds, AdipoR agonist (AdipoRon), bound to both AdipoR1 and AdipoR2 in vitro. AdipoRon showed very similar effects to adiponectin in muscle and liver, such as activation of AMPK and PPAR-α pathways, and ameliorated insulin resistance and glucose intolerance in mice fed a high-fat diet, which was completely obliterated in AdipoR1 and AdipoR2 double-knockout mice. Moreover, AdipoRon ameliorated diabetes of genetically obese rodent model db/db mice, and prolonged the shortened lifespan of db/db mice on a high-fat diet. Thus, orally active AdipoR agonists such as AdipoRon are a promising therapeutic approach for the treatment of obesity-related diseases such as type 2 diabetes.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. J Biol Chem. 1996 Nov 1;271(44):27879-87 - PubMed
    1. Nature. 2010 Apr 29;464(7293):1313-9 - PubMed
    1. FASEB J. 1997 Apr;11(5):346-54 - PubMed
    1. J Biochem. 1996 Oct;120(4):803-12 - PubMed
    1. Nature. 2003 Jun 12;423(6941):762-9 - PubMed

Publication types

MeSH terms

LinkOut - more resources