PSN-375963 is a GPR119 partial agonist. GPR119 is an orphan GPCR, expressed predominantly in pancreas and GI tract, that has been characterized. Its endogenous ligands are oleoylethanolamide (OEA) and oleoyl-lysophosphatidylcholine, lipid signaling molecules that regulate food intake and body weight. OEA decreases food intake, so GPR119 agonists are potential therapies for obesity. Initial studies showed that PSN-375963 has similar potency and partial efficacy compared to OEA. Further studies revealed that although OEA and PSN-375963 are GPR119 agonists, they have divergent effects on insulin secretion, calcium signaling, and cAMP production.
Nutrient-sensing receptors located on enteroendocrine (EEC) cells modulate appetite via detection of luminal contents. Colonic 'tasting' of luminal contents may influence changes to appetite observed in obesity and after weight loss induced by bariatric surgery. We assessed the effects of
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