GLP-1 receptors are involved in the GLP-1 (7-36) amide-induced modulation of glucose homoeostasis, emesis and feeding in Suncus murinus (house musk shrew)

Abstract

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 <i>Suncus murinus</i>. 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.