GPR142 prompts glucagon-like Peptide-1 release from islets to improve β cell function.

•GPR142 is expressed in both α cells and β cells in pancreatic islets.•Stimulation of GPR142 by a selective agonist increases glucagon secretion.•GPR142 agonism promotes glucagon-like peptide-1 release from islets by upregulating prohormone convertase 1/3.•Increases in insulin secretion and content via GPR142 engagement require intact GLP-1 receptor signaling.