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

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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 role1. We have shown that GLP-1 and its specific receptors are present in the hypo-thalamus2,3. 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)4, 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 activation5. 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 feeding6. These findings suggest that central GLP-1 is a new physiological mediator of satiety.

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Author notes

  1. J. Herbert: Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK

  2. S. R Bloom: To whom correspondence should be addressed

Authors and Affiliations

  1. Endocrine Unit, Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London, W12 ONN, UK

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

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  1. M. D. Turton
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  2. D. O'Shea
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  5. C. M. B. Edwards
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Turton, M., O'Shea, D., Gunn, I. et al. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 379, 69–72 (1996). https://doi.org/10.1038/379069a0

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  • DOI: https://doi.org/10.1038/379069a0

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