Abstract | AIM: METHODS: On the basis of a series of dose-finding studies, the doses of exenatide and liraglutide with similar acute anorectic effects were identified. GE was assessed using a standard acetaminophen release assay. After the acute test, rats were dosed bi-daily for 14 days in which period food intake and body weight was monitored. On day 14, the GE rate was reassessed. RESULTS: While both compounds exerted robust acute reductions in GE, the effect was markedly diminished following 14 days of dosing with liraglutide. In contrast, exenatide-treated rats still displayed a profound reduction in GE at the 14-day time-point. Both compounds exerted similar effects on body weight. CONCLUSION: The data suggest that the 'gastric inhibitory' GLP-1 receptors in rats are subject to desensitization/tachyphylaxis but that this effect is dependent on full 24-h exposure as obtained by liraglutide. The body weight-lowering effects of GLP-1 receptor stimulation are not subject to desensitization. These data indicate that regulation of appetite signals in the brain, and not GE, is the main mechanism for liraglutide-induced weight loss.
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Authors | J Jelsing, N Vrang, G Hansen, K Raun, M Tang-Christensen, L Bjerre Knudsen |
Journal | Diabetes, obesity & metabolism
(Diabetes Obes Metab)
Vol. 14
Issue 6
Pg. 531-8
(Jun 2012)
ISSN: 1463-1326 [Electronic] England |
PMID | 22226053
(Publication Type: Journal Article)
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Copyright | © 2012 Blackwell Publishing Ltd. |
Chemical References |
- Peptides
- Venoms
- Liraglutide
- Glucagon-Like Peptide 1
- Exenatide
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Topics |
- Animals
- Appetite Regulation
(drug effects)
- Eating
(drug effects)
- Exenatide
- Gastric Emptying
(drug effects)
- Glucagon-Like Peptide 1
(analogs & derivatives, pharmacokinetics, pharmacology)
- Hippocampus
(drug effects)
- Injections, Intravenous
- Liraglutide
- Male
- Obesity
(drug therapy)
- Peptides
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Venoms
(pharmacology)
- Weight Loss
(drug effects)
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