Action of centrally administered glucagon-like peptide-1 (7-36) amide to modulate blood glucose, feeding and induce emesis in Suncus murinus

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).