Action of centrally administered glucagon-like peptide-1 (7-36) amide to modulate blood glucose, feeding and induce emesis in Suncus murinus
Author(s)
Lu, Zengbing
Author(s)
Rudd, J. A.
Date Issued
2016
Conference
Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) and Molecular Pharmacology of G Protein-Coupled Receptors (MPGPCR) Joint Scientific Meeting
Abstract
Introduction. Glucagon-like peptide-1 (7-36) amide (GLP-1) is released from the gut as an incretin hormone to potentiate glucose-stimulated insulin secretion. GLP-1 is also produced in the central nervous system (CNS) to regulate feeding.
Aims. To examine the potential of central administration of GLP-1 to modulate blood glucose levels, emesis and feeding in Suncus murinus. Methods. To elevate blood glucose levels, anaesthetised fasted animals were administered glucose (5.55 mmol/kg, i.p.) 10 min prior to an infusion of GLP-1 (0.3-10 nmol, i.c.v), or saline (5 µl). Blood glucose levels were measured at 5-20 min intervals for 1 h. In other studies, GLP-1 (0.03-10 nmol, i.c.v.), or saline (5 µl), was administered to conscious fasted animals. Food and water consumption and spontaneous activities were measured for 1 h. Results. The administration of glucose caused a progressive elevation of blood glucose in the saline-treated animals that peaked at 5 min and then decreased gradually afterwards. GLP-1 (10 nmol, i.c.v.) produced a 32.5% reduction in the AUC0-50 values (GLP-1 178.1 ± 47.4 vs. saline 120.1 ± 8.1, P<0.05). In the conscious animals, GLP-1 (0.3 – 10 nmol, i.c.v.) reduced the distance travelled by ~60% (P<0.05), but had no effect on velocity (P>0.05). GLP-1 (0.03–10 nmol, i.c.v.) inhibited food (P<0.05) and water intake (P<0.05) significantly. GLP-1 at 3 and 10 nmol, i.c.v., induced emesis in 1 and 2 animals, respectively. Discussion. GLP-1 (7-36) amide is involved in the modulation of blood glucose levels, locomotor activity, feeding, and emesis in Suncus murinus. The mechanism of GLP-1 to induce emesis and inhibit feeding requires further investigation. These studies were fully supported by a grant from the Research Grants Council of the HKSAR, China (Project no. UGC/FDS11/M02/15).
Aims. To examine the potential of central administration of GLP-1 to modulate blood glucose levels, emesis and feeding in Suncus murinus. Methods. To elevate blood glucose levels, anaesthetised fasted animals were administered glucose (5.55 mmol/kg, i.p.) 10 min prior to an infusion of GLP-1 (0.3-10 nmol, i.c.v), or saline (5 µl). Blood glucose levels were measured at 5-20 min intervals for 1 h. In other studies, GLP-1 (0.03-10 nmol, i.c.v.), or saline (5 µl), was administered to conscious fasted animals. Food and water consumption and spontaneous activities were measured for 1 h. Results. The administration of glucose caused a progressive elevation of blood glucose in the saline-treated animals that peaked at 5 min and then decreased gradually afterwards. GLP-1 (10 nmol, i.c.v.) produced a 32.5% reduction in the AUC0-50 values (GLP-1 178.1 ± 47.4 vs. saline 120.1 ± 8.1, P<0.05). In the conscious animals, GLP-1 (0.3 – 10 nmol, i.c.v.) reduced the distance travelled by ~60% (P<0.05), but had no effect on velocity (P>0.05). GLP-1 (0.03–10 nmol, i.c.v.) inhibited food (P<0.05) and water intake (P<0.05) significantly. GLP-1 at 3 and 10 nmol, i.c.v., induced emesis in 1 and 2 animals, respectively. Discussion. GLP-1 (7-36) amide is involved in the modulation of blood glucose levels, locomotor activity, feeding, and emesis in Suncus murinus. The mechanism of GLP-1 to induce emesis and inhibit feeding requires further investigation. These studies were fully supported by a grant from the Research Grants Council of the HKSAR, China (Project no. UGC/FDS11/M02/15).
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