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© 2002 The American Society for Nutritional Sciences J. Nutr. 132:990-995, 2002

Nutritional Neurosciences

Exendin-4, a GLP-1 Receptor Agonist, Modulates the Effect of Macronutrients on Food Intake by Rats1

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.

The hypothesis that peripheral GLP-1 modulates the effect of macronutrients on food intake in rats was tested by administration of its agonist, exendin-4. The effect of exendin-4 on food intake suppression and blood glucose after carbohydrate, fat and protein preloads was measured. Exendin-4 reduced the effect of glucose preloads on food intake only during the first 30 min (P = 0.01) of feeding, but had a more prolonged effect when given with corn oil (P < 0.01 at 0–0.5 h and 0–1 h, P = 0.055 at 0–2 h, and P = 0.07 at 0–3 h) and whey (P < 0.05 at 0–1 h, P = 0.06 at 0–2 h, and P = 0.07 at 0–3 h) preloads. Blood glucose measured over 2 h was reduced at 15 min when given with glucose (P < 0.01), unchanged when given with corn oil and increased at 60 and 120 min when given with whey (P < 0.01). Thus, the effect of exendin-4 on the feeding response depended on the composition of the macronutrient preloads and seems to be independent of blood glucose concentrations.

KEY WORDS: • agonist • blood glucose • food intake • gut peptide • intraperitoneal administration • rats




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