Glucose-dependent insulinotropic
polypeptide (GIP) and
glucagon-like peptide-2 (GLP-2) are
hormones secreted from the enteroendocrine cells after a meal. They exert their actions through activation of
G protein-coupled receptors (R), the GIPR and GLP-2R, respectively. Both have been reported to influence metabolism. The purpose of the study was to investigate the role of the
hormones in the regulation of
lipid and bone homeostasis by subchronic treatment with novel GIPR and GLP-2R antagonists. Rats were injected once daily with vehicle, GIPR, or GLP-2R antagonists for 3 weeks.
Body weight, food intake, body composition, plasma
lipoprotein lipase (LPL),
adipokines,
triglycerides and the marker of
bone resorption carboxy-terminal
collagen crosslinks (CTX), were examined. In rats, subchronic treatment with GIPR antagonist, rat
GIP (3-30)NH2, did not modify food intake and
bone resorption, but significantly increased
body weight, body fat mass,
triglycerides, LPL, and
leptin levels compared with vehicle treated rats. Subchronic (
Pro3)GIP (a partial GIPR agonist), GLP-2(11-33), and GLP-2(3-33) (GLP-2R antagonists) treatment did not affect any parameter. The present results would be consistent with a role for GIP, but not GLP-2, in the maintenance of
lipid homeostasis in rats, while neither GIPR nor GLP-2R antagonism appeared to influence
bone resorption in rats.