GPR119 is required for C18:1 NAT-stimulated GLP-1 and glucagon secretion. (A) cAMP synthesis assay in CHO cells stably transfected with mouse GPR119; AR231453, synthetic GPR119 agonist (representative curve, in triplicate). Estimated EC50 is shown. (B–D) GLP-1 secretion from organoids generated from duodenum, ileum, and colon from GPR119-KO mice or littermate GPR119-WT (n = 3 separate experiments with 2 to 4 replicates). (E and F) Insulin and glucagon release from isolated human pancreatic islet cells with 10 µM C18:1 NAT or vehicle (DMSO) (2 nondiabetic patients, in quadruplicate). (E and F, Insets) Area under the curve. (G and H) Insulin and glucagon secretion in isolated murine pancreatic islets (3 to 5 experiments in triplicate) at the indicated glucose concentration and arginine (Arg) or amino acid mixture (AA). Data are presented as mean ± SEM. *P < 0.05.