Document Detail


Glucagon-like peptide-1 receptor agonists suppress water intake independent of effects on food intake.
MedLine Citation:
PMID:  21975647     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glucagon-like peptide-1 (GLP-1) is produced by and released from the small intestine following ingestion of nutrients. GLP-1 receptor (GLP-1R) agonists applied peripherally or centrally decrease food intake and increase glucose-stimulated insulin secretion. These effects make the GLP-1 system an attractive target for the treatment of type 2 diabetes mellitus and obesity. In addition to these more frequently studied effects of GLP-1R stimulation, previous reports indicate that GLP-1R agonists suppress water intake. The present experiments were designed to provide greater temporal resolution and site specificity for the effect of GLP-1 and the long-acting GLP-1R agonists, exendin-4 and liraglutide, on unstimulated water intake when food was and was not available. All three GLP-1R ligands suppressed water intake after peripheral intraperitoneal administration, both in the presence of and the absence of food; however, the magnitude and time frame of water intake suppression varied by drug. GLP-1 had an immediate, but transient, hypodipsic effect when administered peripherally, whereas the water intake suppression by IP exendin-4 and liraglutide was much more persistent. Additionally, intracerebroventricular administration of GLP-1R agonists suppressed water intake when food was absent, but the suppression of intake showed modest differences depending on whether the drug was administered to the lateral or fourth ventricle. To the best of our knowledge, this is the first demonstration of GLP-1 receptor agonists affecting unstimulated, overnight intake in the absence of food, the first test for antidipsogenic effects of hindbrain application of GLP-1 receptor agonists, and the first test of a central effect (forebrain or hindbrain) of liraglutide on water intake. Overall, these results show that GLP-1R agonists have a hypodipsic effect that is independent of GLP-1R-mediated effects on food intake, and this occurs, in part, through central nervous system GLP-1R activation.
Authors:
Naomi J McKay; Scott E Kanoski; Matthew R Hayes; Derek Daniels
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-10-05
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  301     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-06     Completed Date:  2012-02-14     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1755-64     Citation Subset:  IM    
Affiliation:
Behavioral Neuroscience Program, Department of Psychology, The State University of New York at Buffalo, Buffalo, New York 14260, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Drinking / drug effects*
Eating / drug effects*
Glucagon-Like Peptide 1 / analogs & derivatives*,  pharmacology*
Male
Peptides / pharmacology*
Rats
Rats, Sprague-Dawley
Receptors, Glucagon / agonists*
Time Factors
Venoms / pharmacology*
Grant Support
ID/Acronym/Agency:
DK085435/DK/NIDDK NIH HHS; DK089752/DK/NIDDK NIH HHS; HL0919/HL/NHLBI NIH HHS; R01 HL091911/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
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
Comments/Corrections

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


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