Document Detail


The GLP-1 agonist exendin-4 reduces food intake in nonhuman primates through changes in meal size.
MedLine Citation:
PMID:  17581835     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Exendin-4 (Ex4), a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce food intake and suppress gastric emptying in rodents and humans. In this study we investigated the effects of peripheral administration of Ex4 on food intake and meal patterns in adult male rhesus macaques. Rhesus macaques (n = 4) that had been trained to lever press for food pellets were injected intramuscularly 15 min before the start of their 6-h daily feeding period. Ex4 was given at doses of 0.10, 0.32, 0.56, 1.0, and 3.0 microg/kg. Ex4 suppressed food intake in a dose-dependent manner, with the 3.0 microg/kg dose completely preventing feeding during the 6-h period and the 0.10 microg/kg dose suppressing intake by 17%. Doses of 0.32, 0.56, 1.0, and 3.0 microg/kg caused significant reductions in cumulative intake at all six hourly time points. Ex4 inhibited food intake through a specific effect on meal size. Meal size was significantly reduced in a dose-dependent manner with significant reductions at the 0.32 and 1.0 microg/kg doses (P < 0.05). Day 2 and 3 intakes returned to baseline levels with no compensation for Ex4-induced feeding suppression. Administration of doses of 0.32 and 0.56 microg/kg Ex4 over 5 consecutive days led to sustained reductions in intake with no evidence of compensation. Again, these reductions were due to specific effects on meal size. These results demonstrate that activation of GLP-1 pathways has potent effects on the controls of meal size and overall food intake in a nonhuman primate model.
Authors:
Karen A Scott; Timothy H Moran
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-06-20
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  293     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-31     Completed Date:  2007-10-17     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R983-7     Citation Subset:  IM    
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Data Interpretation, Statistical
Dose-Response Relationship, Drug
Eating / drug effects*,  psychology*
Feeding Behavior / drug effects*
Glucagon-Like Peptide 1 / agonists*
Macaca mulatta
Male
Peptides / administration & dosage,  pharmacology*
Venoms / administration & dosage,  pharmacology*
Grant Support
ID/Acronym/Agency:
DK 19302/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Peptides; 0/Venoms; 141732-76-5/exenatide; 89750-14-1/Glucagon-Like Peptide 1
Comments/Corrections
Comment In:
Am J Physiol Regul Integr Comp Physiol. 2007 Sep;293(3):R981-2   [PMID:  17596320 ]

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


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