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)

Author(s)
Lu, Zengbing
Author(s)
Tu, L.
Ngan, M. P.
Rudd, J. A.
Date Issued
2020
Publisher
Elsevier
Journal
European Journal of Pharmacology
Volume
888
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 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.
URI
DOI
SFU Affiliated Publication
Yes
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