Document Detail


Peripheral and central GLP-1 receptor populations mediate the anorectic effects of peripherally administered GLP-1 receptor agonists, liraglutide and exendin-4.
MedLine Citation:
PMID:  21693680     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The long-acting glucagon-like peptide-1 receptor (GLP-1R) agonists, exendin-4 and liraglutide, suppress food intake and body weight. The mediating site(s) of action for the anorectic effects produced by peripheral administration of these GLP-1R agonists are not known. Experiments addressed whether food intake suppression after i.p. delivery of exendin-4 and liraglutide is mediated exclusively by peripheral GLP-1R or also involves direct central nervous system (CNS) GLP-1R activation. Results showed that CNS delivery [third intracerebroventricular (3(rd) ICV)] of the GLP-1R antagonist exendin-(9-39) (100 μg), attenuated the intake suppression by i.p. liraglutide (10 μg) and exendin-4 (3 μg), particularly at 6 h and 24 h. Control experiments show that these findings appear to be based neither on the GLP-1R antagonist acting as a nonspecific competing orexigenic signal nor on blockade of peripheral GLP-1R via efflux of exendin-(9-39) to the periphery. To assess the contribution of GLP-1R expressed on subdiaphragmatic vagal afferents to the anorectic effects of liraglutide and exendin-4, food intake was compared in rats with complete subdiaphragmatic vagal deafferentation and surgical controls after i.p. delivery of the agonists. Both liraglutide and exendin-4 suppressed food intake at 3 h, 6 h, and 24 h for controls; for subdiaphragmatic vagal deafferentation rats higher doses of the GLP-1R agonists were needed for significant food intake suppression, which was observed at 6 h and 24 h after liraglutide and at 24 h after exendin-4. Conclusion: Food intake suppression after peripheral administration of exendin-4 and liraglutide is mediated by activation of GLP-1R expressed on vagal afferents as well as direct CNS GLP-1R activation.
Authors:
Scott E Kanoski; Samantha M Fortin; Myrtha Arnold; Harvey J Grill; Matthew R Hayes
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-06-21
Journal Detail:
Title:  Endocrinology     Volume:  152     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-25     Completed Date:  2011-09-21     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3103-12     Citation Subset:  AIM; IM    
Affiliation:
Department of Psychology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. kanoski@sas.upenn.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Appetite Depressants / pharmacology*
Body Weight / drug effects
Brain / physiology*
Calcitonin / pharmacology
Eating / drug effects
Glucagon-Like Peptide 1 / analogs & derivatives*,  pharmacology
Male
Peptide Fragments / pharmacology
Peptides / pharmacology*
Rats
Rats, Sprague-Dawley
Receptors, Glucagon / agonists,  physiology*
Vagus Nerve / physiology
Venoms / pharmacology*
Grant Support
ID/Acronym/Agency:
DK085435/DK/NIDDK NIH HHS; DK089752/DK/NIDDK NIH HHS; DK21397/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Appetite Depressants; 0/Peptide Fragments; 0/Peptides; 0/Receptors, Glucagon; 0/Venoms; 0/glucagon-like peptide-1 receptor; 133514-43-9/exendin (9-39); 141732-76-5/exenatide; 47931-85-1/salmon calcitonin; 839I73S42A/liraglutide; 89750-14-1/Glucagon-Like Peptide 1; 9007-12-9/Calcitonin
Comments/Corrections

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