Repeated intracerebroventricular administration of glucagon-like peptide-1-(7-36) amide or exendin-(9-39) alters body weight in the rat.
Central nervous system glucagon-like peptide-1-(7-36) amide (GLP-1) administration has been reported to acutely reduce food intake in the rat. We here report that repeated intracerebroventricular (i.c.v.) injection of GLP-1 or the GLP-1 receptor antagonist, exendin-(9-39), affects food intake and body weight. Daily i.c.v. injection of 3 nmol GLP-1 to schedule-fed rats for 6 days caused a reduction in food intake and a decrease in body weight of 16 +/- 5 g (P < 0.02 compared with saline-injected controls). Daily i.c.v. administration of 30 nmol exendin-(9-39) to schedule-fed rats for 3 days caused an increase in food intake and increased body weight by 7 +/- 2 g (P < 0.02 compared with saline-injected controls). Twice daily i.c.v. injections of 30 nmol exendin-(9-39) with 2.4 nmol neuropeptide Y to ad libitum-fed rats for 8 days increased food intake and increased body weight by 28 +/- 4 g compared with 14 +/- 3 g in neuropeptide Y-injected controls (P < 0.02). There was no evidence of tachyphylaxis in response to i.c.v. GLP-1 or exendin-(9-39). GLP-1 may thus be involved in the regulation of body weight in the rat.
Meeran
K
K
Imperial College School of Medicine Endocrine Unit, Hammersmith Hospital, London, United Kingdom.
O'Shea
D
D
Edwards
C M
CM
Turton
M D
MD
Heath
M M
MM
Gunn
I
I
Abusnana
S
S
Rossi
M
M
Small
C J
CJ
Goldstone
A P
AP
Taylor
G M
GM
Sunter
D
D
Steere
J
J
Choi
S J
SJ
Ghatei
M A
MA
Bloom
S R
SR
D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D002149:Energy Intake / Q000187:drug effects; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D007276:Injections, Intraventricular; D008297:Male; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018377:Neurotransmitter Agents; D010446:Peptide Fragments; C055453:glucagon-like peptide 1 (7-36)amide; C083773:exendin (9-39); D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon