Document Detail


The role of nausea in food intake and body weight suppression by peripheral GLP-1 receptor agonists, exendin-4 and liraglutide.
MedLine Citation:
PMID:  22227019     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The FDA-approved glucagon-like-peptide-1 receptor (GLP-1R) agonists exendin-4 and liraglutide reduce food intake and body weight. Nausea is the most common adverse side effect reported with these GLP-1R agonists. Whether food intake suppression by exendin-4 and liraglutide occurs independently of nausea is unknown. Further, the neurophysiological mechanisms mediating the nausea associated with peripheral GLP-1R agonist use are poorly understood. Using two established rodent models of nausea [conditioned taste avoidance (CTA) and pica (ingestion of nonnutritive substances)], results show that all peripheral doses of exendin-4 that suppress food intake also produce CTA, whereas one dose of liraglutide suppresses intake without producing CTA. Chronic (12 days) daily peripheral administration of exendin-4 produces a progressive increase in pica coupled with stable, sustained food intake and body weight suppression, whereas the pica response and food intake reduction by daily liraglutide are more transient. Results demonstrate that the nausea response accompanying peripheral exendin-4 occurs via a vagal-independent pathway involving GLP-1R activation in the brain as the exendin-4-induced pica response is attenuated with CNS co-administration of the GLP-1R antagonist exendin-(9-39), but not by vagotomy. Direct administration of exendin-4 to the medial subnucleus of the nucleus tractus solitarius (mNTS), but not to the central nucleus of the amygdala, reduced food intake and produced a pica response, establishing the mNTS as a potential GLP-1R-expressing site mediating nausea responses associated with GLP-1R agonists.
Authors:
Scott E Kanoski; Laura E Rupprecht; Samantha M Fortin; Bart C De Jonghe; Matthew R Hayes
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-28
Journal Detail:
Title:  Neuropharmacology     Volume:  62     ISSN:  1873-7064     ISO Abbreviation:  Neuropharmacology     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-02-13     Completed Date:  2012-07-23     Revised Date:  2013-05-13    
Medline Journal Info:
Nlm Unique ID:  0236217     Medline TA:  Neuropharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  1916-27     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Psychology, School of Art and Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Weight / drug effects*,  physiology
Eating / drug effects*,  physiology
Glucagon-Like Peptide 1 / analogs & derivatives*,  toxicity
Hypoglycemic Agents / toxicity*
Male
Nausea / chemically induced*,  physiopathology
Peptides / toxicity*
Rats
Rats, Sprague-Dawley
Receptors, Glucagon / agonists*
Solitary Nucleus / drug effects,  physiopathology
Vagus Nerve / drug effects,  physiopathology
Venoms / toxicity*
Grant Support
ID/Acronym/Agency:
DK085435/DK/NIDDK NIH HHS; DK089752/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Hypoglycemic Agents; 0/Peptides; 0/Receptors, Glucagon; 0/Venoms; 0/glucagon-like peptide-1 receptor; 141732-76-5/exenatide; 839I73S42A/liraglutide; 89750-14-1/Glucagon-Like Peptide 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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