A role for glucagon-like peptide-1 in the central regulation of feeding - PubMed (original) (raw)

. 1996 Jan 4;379(6560):69-72.

doi: 10.1038/379069a0.

D O'Shea, I Gunn, S A Beak, C M Edwards, K Meeran, S J Choi, G M Taylor, M M Heath, P D Lambert, J P Wilding, D M Smith, M A Ghatei, J Herbert, S R Bloom

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A role for glucagon-like peptide-1 in the central regulation of feeding

M D Turton et al. Nature. 1996.

Abstract

The sequence of glucagon-like peptide-1 (7-36) amide (GLP-1) is completely conserved in all mammalian species studied, implying that it plays a critical physiological role. We have shown that GLP-1 and its specific receptors are present in the hypothalamus. No physiological role for central GLP-1 has been established. We report here that intracerebroventricular (ICV) GLP-1 powerfully inhibits feeding in fasted rats. ICV injection of the specific GLP-1-receptor antagonist, exendin (9-39), blocked the inhibitory effect of GLP-1 on food intake. Exendin (9-39) alone had no influence on fast-induced feeding but more than doubled food intake in satiated rats, and augmented the feeding response to the appetite stimulant, neuropeptide Y. Induction of c-fos is a marker of neuronal activation. Following ICV GLP-1 injection, c-fos appeared exclusively in the paraventricular nucleus of the hypothalamus and central nucleus of the amygdala, and this was inhibited by prior administration of exendin (9-39). Both of these regions of the brain are of primary importance in the regulation of feeding. These findings suggest that central GLP-1 is a new physiological mediator of satiety.

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