Document Detail


Comparative effects of the long-acting GLP-1 receptor ligands, liraglutide and exendin-4, on food intake and body weight suppression in rats.
MedLine Citation:
PMID:  21415845     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The glucagon-like-peptide-1 receptor (GLP-1R) agonists, liraglutide (Victoza) and the synthetic product of exendin-4 (Byetta), are approved for type II diabetes mellitus (T2DM) treatment and may be efficacious in obesity treatment as well, in part, due to the drugs' resistance to enzymatic degradation and prolonged half-life relative to endogenous GLP-1. To address the need to directly compare the food intake- and body weight-suppressive effects of these two GLP-1R ligands, acute and chronic dosing experiments were performed. Once-daily (q.d.) exendin-4 (0, 0.33, 1.5, and 3.0 µg/kg) and liraglutide (0, 50, 100, and 300 µg/kg, q.d.) both reduced the chow intake in nonobese rats in a dose-dependent fashion following either intraperitoneal (IP) or subcutaneous (SC) administration, whereas only liraglutide reduced 24 and 48 h body weight in nonobese, chow-maintained rats. Chow intake and body weight suppression by liraglutide were of greater magnitude and shorter latency following IP compared to SC delivery, whereas for exendin-4, the magnitude of intake-suppression was similar for IP and SC administration. The effects of chronic delivery (7 consecutive days; IP) of liraglutide (25 and 50 µg/kg; q.d.) and exendin-4 (3 µg/kg; q.d. and twice-daily (b.i.d.)) on food intake and body weight were also examined in diet-induced obese (DIO) rats. Liraglutide (50 µg/kg q.d.) and exendin-4 (3 µg/kg b.i.d.) were comparable in suppressing overall high fat/sucrose diet (HFS; 60% kcal from fat) intake. Both drugs regimens yielded marked weight loss over the 7-day period. The weight loss effect of liraglutide was achieved in the first 2 days and remained stable for the duration of the experiment; weight loss with exendin-4 appeared more linear over the 7-day period. In conclusion, administration of the GLP-1R ligands, exendin-4 (b.i.d.) and liraglutide (q.d.), lead to comparable and pronounced suppression of food intake and body weight in DIO rats, suggesting a potential role for these drugs as a clinical tool for obesity treatment.
Authors:
Matthew R Hayes; Scott E Kanoski; Amber L Alhadeff; Harvey J Grill
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-17
Journal Detail:
Title:  Obesity (Silver Spring, Md.)     Volume:  19     ISSN:  1930-739X     ISO Abbreviation:  Obesity (Silver Spring)     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-27     Completed Date:  2011-11-08     Revised Date:  2013-05-13    
Medline Journal Info:
Nlm Unique ID:  101264860     Medline TA:  Obesity (Silver Spring)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1342-9     Citation Subset:  IM    
Affiliation:
Department of Psychology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. hayesmr@sas.upenn.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Obesity Agents / administration & dosage,  therapeutic use*
Appetite Regulation / drug effects*
Dietary Fats / adverse effects
Dietary Sucrose / adverse effects
Dose-Response Relationship, Drug
Glucagon-Like Peptide 1 / administration & dosage,  agonists,  analogs & derivatives*,  therapeutic use
Hypoglycemic Agents / administration & dosage,  therapeutic use*
Injections, Intraperitoneal
Injections, Subcutaneous
Ligands
Male
Obesity / drug therapy
Peptides / administration & dosage,  therapeutic use*
Rats
Rats, Sprague-Dawley
Receptors, Glucagon / agonists*
Time Factors
Venoms / administration & dosage,  therapeutic use*
Weight Loss / drug effects*
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/Anti-Obesity Agents; 0/Dietary Fats; 0/Dietary Sucrose; 0/Hypoglycemic Agents; 0/Ligands; 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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