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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0453v1 201/2/219    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lan, H. Articles by Kowalski, T. Search for Related Content PubMed PubMed Citation Articles by Lan, H. Articles by Kowalski, T.

H Lan, Cardiovascular and Metabolic Disease Research, Schering-Plough Research Institute, Kenilworth, 07033, United States
G Vassileva, Discovery Technologies, Schering-Plough Research Institute, kenilworth, United States
A Corona, Cardiovascular & Metabolic Disease Research, Schering-Plough Research Institute, Kenilworth, United States
L Liu, Cardiovascular & Metabolic Disease Research, Schering-Plough Research Institute, Kenilworth, United States
H Baker, Cardiovascular & Metabolic Disease Research, Schering-Plough Research Institute, Kenilworth, United States
A Golovko, Discovery Technologies, Schering-Plough Research Institute, kenilworth, United States
S Abbondanzo, Discovery Technologies, Schering-Plough Research Institute, kenilworth, United States
W Hu, Discovery Technologies, Schering-Plough Research Institute, kenilworth, United States
S Yang, Discovery Technologies, Schering-Plough Research Institute, kenilworth, United States
Y Ning, Cardiovascular & Metabolic Disease Research, Schering-Plough Research Institute, Kenilworth, United States
R Del Vecchio, Discovery Technologies, Schering-Plough Research Institute, kenilworth, United States
F Poulet, Drug Safety, Schering-Plough Research Institute, Kenilworth, United States
M Laverty, Discovery Technologies, Schering-Plough Research Institute, kenilworth, United States
E Gustafson, Discovery Technologies, Schering-Plough Research Institute, kenilworth, United States
J Hedrick, Cardiovascular & Metabolic Disease Research, Schering-Plough Research Institute, Kenilworth, United States
T Kowalski, Cardiovascular and Metabolic Disease Research, Schering-Plough Research Institute, Kenilworth, United States

Correspondence: Hong Lan, Email: hong.lan{at}spcorp.com

Abstract

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