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
. 2009 Oct;5(10):749-57.
doi: 10.1038/nchembio.209. Epub 2009 Jul 13.

A new glucagon and GLP-1 co-agonist eliminates obesity in rodents

Jonathan W Day  1 , Nickki Ottaway, James T Patterson, Vasily Gelfanov, David Smiley, Jas Gidda, Hannes Findeisen, Dennis Bruemmer, Daniel J Drucker, Nilika Chaudhary, Jenna Holland, Jazzminn Hembree, William Abplanalp, Erin Grant, Jennifer Ruehl, Hilary Wilson, Henriette Kirchner, Sarah Haas Lockie, Susanna Hofmann, Stephen C Woods, Ruben Nogueiras, Paul T Pfluger, Diego Perez-Tilve, Richard DiMarchi, Matthias H Tschöp
Affiliations

A new glucagon and GLP-1 co-agonist eliminates obesity in rodents

Jonathan W Day et al. Nat Chem Biol. 2009 Oct.

Abstract

We report the efficacy of a new peptide with agonism at the glucagon and GLP-1 receptors that has potent, sustained satiation-inducing and lipolytic effects. Selective chemical modification to glucagon resulted in a loss of specificity, with minimal change to inherent activity. The structural basis for the co-agonism appears to be a combination of local positional interactions and a change in secondary structure. Two co-agonist peptides differing from each other only in their level of glucagon receptor agonism were studied in rodent obesity models. Administration of PEGylated peptides once per week normalized adiposity and glucose tolerance in diet-induced obese mice. Reduction of body weight was achieved by a loss of body fat resulting from decreased food intake and increased energy expenditure. These preclinical studies indicate that when full GLP-1 agonism is augmented with an appropriate degree of glucagon receptor activation, body fat reduction can be substantially enhanced without any overt adverse effects.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Am J Physiol. 1987 Jan;252(1 Pt 2):R160-5 - PubMed
    1. Biochemistry. 2001 Nov 6;40(44):13188-200 - PubMed
    1. Comp Biochem Physiol. 1965 Dec;16(4):367-81 - PubMed
    1. Gastroenterology. 2004 Aug;127(2):546-58 - PubMed
    1. Br J Pharmacol. 2003 Mar;138(5):787-94 - PubMed

MeSH terms

LinkOut - more resources

  NODES
admin 2
twitter 2