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Endocrinology Vol. 140, No. 1 244-250
Copyright © 1999 by The Endocrine Society

ARTICLES

Repeated Intracerebroventricular Administration of Glucagon-Like Peptide-1-(7–36) Amide or Exendin-(9–39) Alters Body Weight in the Rat1

Karim Meeran2, Donal O’Shea3, C. Mark B. Edwards4, Mandy D. Turton, Melanie M. Heath5, Irene Gunn, Salahedeen Abusnana, Michela Rossi, Caroline J. Small6, Anthony P. Goldstone2, Gillian M. Taylor5, David Sunter, Joanna Steere, Sang Jeon Choi, Mohammad A. Ghatei and Stephen R. Bloom

Imperial College School of Medicine Endocrine Unit, Hammersmith Hospital, London, United Kingdom W12 0NN

Address all correspondence and requests for reprints to: Prof. S. R. Bloom, ICSM Endocrine Unit, Hammersmith Hospital, Du Cane Road, London, United Kingdom W12 0HS. E-mail: sbloom{at}rpms.ac.uk

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 (icv) injection of GLP-1 or the GLP-1 receptor antagonist, exendin-(9–39), affects food intake and body weight. Daily icv 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 icv 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 icv 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 icv GLP-1 or exendin-(9–39). GLP-1 may thus be involved in the regulation of body weight in the rat.




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