G protein-coupled receptor 119 (GPR119) (GPR119)

G protein-coupled receptor 119 (GPR119) is a Class A G protein-coupled receptor primarily expressed in pancreatic beta-cells and intestinal enteroendocrine cells, such as L-cells and K-cells [1, 11]. It functions as a glucose-dependent insulinotropic receptor, meaning its activation enhances insulin secretion specifically in response to elevated blood glucose levels, which minimizes the risk of hypoglycemia [3, 6]. The receptor is activated by endogenous lipid ligands, including oleoylethanolamide (OEA) and lysophosphatidylcholine (LPC) [6, 10]. Upon activation, GPR119 stimulates the production of intracellular cyclic AMP (cAMP) via Gs protein coupling, leading to the release of insulin and incretin hormones like glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) [1, 4, 7]. These actions contribute to improved glycemic control, reduced food intake, and potential beta-cell preservation, making GPR119 a prominent therapeutic target for type 2 diabetes and obesity [1, 3, 5]. However, clinical development of GPR119 agonists has been challenging, with many candidates failing in Phase II trials due to limited efficacy or desensitization (tachyphylaxis) after repeated dosing [8, 13, 17].

Other names

Glucose-dependent insulinotropic receptorGPCR2hGPCR2SNORF25RUP319AJOSGPR116

GPR119 agonist