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© 2003 The American Society for Nutritional Sciences J. Nutr. 133:2326-2330, July 2003


Nutritional Neurosciences

Exendin-4, a GLP-1 Receptor Agonist, Interacts with Proteins and Their Products of Digestion to Suppress Food Intake in Rats

Alfred Aziz and G. Harvey Anderson2

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 3E2

2To whom correspondence should be addressed. E-mail: harvey.anderson{at}utoronto.ca.

This study investigated the hypotheses that dietary proteins suppress food intake partly through the glucagon-like peptide-1 (GLP-1) signaling pathway, and that this effect is mediated by products of protein digestion. The GLP-1 receptor agonist, Exendin-4 (Ex-4) (0.5 µg/rat), was given intraperitoneally to male Wistar rats, and food intake was measured when Ex-4 was given alone or with preloads of intact whey and casein proteins, their hydrolysates and amino acid mixtures (0.5 g · 4 mL-1 · rat-1). Both Ex-4 and the preloads suppressed food intake (P < 0.05), but the effect of Ex-4 on food intake was reduced when coadministered with the preloads (P < 0.05). Because the effect of Ex-4 was reduced by the protein hydrolysates and by the amino acid preloads, the results support a role for the end products of protein digestion and GLP-1 release in the suppression of food intake in response to protein ingestion. We concluded that the GLP-1 signaling pathway, activated by the release of products of protein digestion, is another mechanism accounting for the reduction of food intake after protein ingestion.


KEY WORDS: • agonist • amino acids • food intake • gut hormone • protein




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