GPR142 Controls Tryptophan-Induced Insulin and Incretin Hormone Secretion to Improve Glucose Metabolism

• Published in: PloS one Vol. 11; no. 6; p. e0157298
• Main Authors: Lin, Hua V, Efanov, Alexander M, Fang, Xiankang, Beavers, Lisa S, Wang, Xuesong, Wang, Jingru, Gonzalez Valcarcel, Isabel C, Ma, Tianwei
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.06.2016; Public Library of Science (PLoS)
• Subjects: Amino acids; Analysis; Animals; Biology and Life Sciences; Blood Glucose; Care and treatment; Chemoreception; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Gastrointestinal tract; GIP protein; Glucose; Glucose - genetics; Glucose - metabolism; Homeostasis; Hormones; Humans; Incretins - genetics; Incretins - metabolism; Influence; Insulin; Insulin - genetics; Insulin - metabolism; Insulin resistance; Insulin Secretion; Insulin-Secreting Cells; Islets of Langerhans - metabolism; Laboratories; Medicine and Health Sciences; Metabolism; Metabolites; Mice; Mice, Knockout; Pancreas; Phenylalanine; Phenylalanine - administration & dosage; Phenylalanine - metabolism; Physical Sciences; Physiology; Polypeptides; R&D; Receptors, G-Protein-Coupled - agonists; Receptors, G-Protein-Coupled - drug effects; Receptors, G-Protein-Coupled - genetics; Research & development; Rodents; Secretion; Signaling; Tryptophan; Tryptophan - administration & dosage; Tryptophan - metabolism; Type 2 diabetes; Indiana; United States > US; China; Indianapolis Indiana
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0157298

GPR142, a putative amino acid receptor, is expressed in pancreatic islets and the gastrointestinal tract, but the ligand affinity and physiological role of this receptor remain obscure. In this study, we show that in addition to L-Tryptophan, GPR142 signaling is also activated by L-Phenylalanine but not by other naturally occurring amino acids. Furthermore, we show that Tryptophan and a synthetic GPR142 agonist increase insulin and incretin hormones and improve glucose disposal in mice in a GPR142-dependent manner. In contrast, Phenylalanine improves in vivo glucose disposal independently of GPR142. Noteworthy, refeeding-induced elevations in insulin and glucose-dependent insulinotropic polypeptide are blunted in Gpr142 null mice. In conclusion, these findings demonstrate GPR142 is a Tryptophan receptor critically required for insulin and incretin hormone regulation and suggest GPR142 agonists may be effective therapies that leverage amino acid sensing pathways for the treatment of type 2 diabetes.