G protein-coupled receptor 142 (GPR142)

GPR142 is an orphan G protein-coupled receptor predominantly expressed in pancreatic β cells, with additional expression in a subset of α cells and the gastrointestinal tract. It acts as a nutrient sensor for certain amino acids, especially L-Tryptophan and L-Phenylalanine, and stimulation enhances glucose-dependent insulin secretion from pancreatic islets. GPR142 agonists are being investigated as novel treatments for type 2 diabetes due to their ability to potentiate glucose-stimulated insulin secretion, enhance incretin hormone release, and improve overall glucose metabolism without increasing hypoglycemia risk.

Activation of GPR142 by agonists leads to increased cAMP levels via PKA/Epac signaling pathways, enhancing glucose-dependent insulin secretion and incretin hormone release.