GPR119 is required for physiological regulation of glucagon-like peptide-1 secretion but not for metabolic homeostasis

• DOI: 10.1677/joe-08-0453
• Publication Date: 2009-03-13T00:34:36Z
• Authors: Hong Lan; Galya Vassileva; Aaron Corona; Li Liu; Hana Baker; Andrei Golovko; Susan J Abbondanzo; Weiwen Hu; Shijun Yang; Yun Ning; Robert A Del Vecchio; Frederique Poulet; Maureen Laverty; Eric L Gustafson; Joseph A Hedrick; Timothy J Kowalski
• Keywords: Incretin; Hyperinsulinemia

G protein-coupled receptor 119 (GPR119) is expressed in pancreatic islets and intestine, involved insulin incretin hormone release. GPR119-knockout (Gpr119(-/-)) mice were reported to have normal islet morphology size, body weight (BW), fed/fasted glucose levels. However, the physiological function of GPR119 its role maintaining homeostasis under metabolic stress remain unknown. Here, we report phenotypes an independently generated line Gpr119(-/-) basal high-fat diet (HFD)-induced obesity. Under low-fat feeding, show plasma lipids, but lower BWs post-prandial levels active glucagon-like peptide 1 (GLP-1). Nutrient-stimulated GLP-1 release attenuated mice, suggesting that plays a regulation secretion. HFD-feeding, both Gpr119(+)(/)(+) gain similarly, develop hyperinsulinemia hyperleptinemia, not hyperglycemia or dyslipidemia. Glucose tolerance tests did reveal genotypic difference. These data essential for maintenance homeostasis. Moreover, found oleoylethanolamide (OEA), as ligand GPR119, was able suppress food intake indicating required hypophagic effect OEA. Our results demonstrate important secretion, appetite suppression.