| Peripheral and central GLP-1 receptor populations mediate the anorectic effects of peripherally administered GLP-1 receptor agonists, liraglutide and exendin-4. | |
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MedLine Citation:
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PMID: 21693680 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Scott E Kanoski; Samantha M Fortin; Myrtha Arnold; Harvey J Grill; Matthew R Hayes |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-06-21 |
Journal Detail:
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Title: Endocrinology Volume: 152 ISSN: 1945-7170 ISO Abbreviation: Endocrinology Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-07-25 Completed Date: 2011-09-21 Revised Date: 2013-05-13 |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
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Languages: eng Pagination: 3103-12 Citation Subset: AIM; IM |
Affiliation:
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Department of Psychology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. kanoski@sas.upenn.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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DK085435/DK/NIDDK NIH HHS; DK089752/DK/NIDDK NIH HHS; DK21397/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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