ECE2018 Guided Posters Diabetes Translational (12 abstracts)
Few studies have investigated the intracellular signaling pathways mediating the effects of glucagon-like peptide-1 (GLP-1) secretagogues in enteroendocrine L cells. Specific receptors, channels, and intracellular signaling proteins expressed by the L cells have only begun to be characterized. The present study aimed to investigate the role of the olfactory receptor (OR) OR51E1 in GLP-1 secretion. We verified the expression of olfactory marker protein (OMP), an indicator of OR-mediated events in non-olfactory systems, in human intestinal L cells. Furthermore, we analyzed OMP and OR51E1 expression in the human L cell line NCI-H716. To investigate whether odorant-activated OR signaling stimulates GLP-1 secretion, we employed nonanoic acid, a known OR51E1 ligand. Treatment with 100 μM nonanoic acid increased GLP-1 secretion by 2.09±0.39 folds; however, this effect was ameliorated on OR51E1 knockdown. Oral administration of nonanoic acid to rats resulted in a 2.89±0.53-fold increase in circulating GLP-1 levels and reductions in blood glucose levels compared to those in the control group. Our findings suggest that nonanoic acid stimulates GLP-1 secretion via OR51E1 signaling in intestinal L cells, thereby indicating an essential role of OR-mediated events and the corresponding odorants in GLP-1 secretion.