A role for glucagon-like peptide-1 in the central regulation of feeding.
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.
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
M D
MD
Turton
D
D
O'Shea
I
I
Gunn
S A
SA
Beak
C M
CM
Edwards
K
K
Meeran
S J
SJ
Choi
G M
GM
Taylor
M M
MM
Heath
P D
PD
Lambert
J P
JP
Wilding
D M
DM
Smith
M A
MA
Ghatei
J
J
Herbert
S R
SR
Bloom
D000818:Animals; D002552:Cerebral Ventricles / Q000502:physiology*; D004435:Eating / Q000502:physiology*; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D007276:Injections, Intraventricular; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D012527:Satiation / Q000502:physiology
D009478:Neuropeptide Y; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; C055453:glucagon-like peptide 1 (7-36)amide; C083773:exendin (9-39); D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon