glucagon-like-peptide-1-(7-36)amide and Vomiting

GLP-1 receptor agonists are used for the treatment of type 2 diabetes but they may reduce appetite and cause nausea and emesis. We investigated if GLP-1 (7-36) amide can modulate glucose homoeostasis, emesis and feeding via an exendin (9-39)-sensitive mechanism in Suncus murinus. The effect of GLP-1 (7-36) amide on glucose homeostasis was examined using an intraperitoneal glucose tolerance test. In conscious fasted animals, food and water consumption and behavior were measured for 1 h following drug administration. c-Fos expression in the brain was measured using immunohistochemistry. GLP-1 (7-36) amide reduced blood glucose levels dose-dependently. Exendin (9-39) did not modify blood glucose levels but suppressed the glucose-lowering effect of GLP-1 (7-36) amide. GLP-1 (7-36) amide inhibited food and water intake, induced emesis and elevated c-Fos expression in the brainstem and hypothalamic nuclei in the brain. Exendin (9-39) antagonised the inhibition of food and water intake and emesis induced by GLP-1 (7-36) amide and the effects on c-Fos expression in the hypothalamus and brainstem, excepting for the bed nucleus of the stria terminalis. These data suggest that the action of GLP-1 (7-36) amide to modulate blood glucose, suppress food and water intake and induce emesis involve GLP-1 receptors in the hypothalamus and brainstem.

Topics: Animals; Blood Glucose; Dose-Response Relationship, Drug; Feeding Behavior; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Homeostasis; Injections, Intraventricular; Male; Peptide Fragments; Shrews; Vomiting