Glucose-dependent insulinotropic receptor (IPR028336)

Short name: GPR119

Overlapping homologous superfamilies


Family relationships


Several 7TM receptors have been cloned but their endogenous ligands are unknown; these have been termed orphan receptors. However, recent research has identified certain pharmacological targets that could be investigated to find, for example, new potential cannabinoid receptors or channels [PMID: 21079038, PMID: 17906678, PMID: 20117132]. GPR18 IPR028335 [PMID: 21595653, PMID: 20346144], GPR55 IPR028334 [PMID: 17876302, PMID: 17876300], GPR119 IPR028336 [PMID: 20117132] show little structural similarity to CB1 and CB2 receptors, but they respond to endogenous agents analogous to the endogenous cannabinoid ligands, as well as some natural/synthetic cannabinoid receptor ligands [PMID: 21079038]. However, because they do not fulfill all of the cannabinoid receptor criteria defined by IUPHAR, the classification of these proteins remains a contentious issue due to conflicting pharmacological results. As a result, they remain classified as putative endogenous agonists by IUPHAR [PMID: 21079038].

This entry represents glucose-dependent insulinotropic receptor, also known as G protein-coupled receptor 119. It is expressed predominantly in the pancreas and gastrointestinal tract in rodents and humans, as well as in the brain in rodents [PMID: 16517404]. It has been shown to be involved in the control of glucose-dependent insulin release and glucagon-like peptide 1 release, respectively [PMID: 15607732, PMID: 17289847], which caused a reduction in food intake and body weight gain in rats [PMID: 16517404]. GPR119 has also been shown to regulate incretin and insulin hormone secretion [PMID: 18724386, PMID: 19009545, PMID: 19282326], behaving as a glucose-dependent insulinotropic receptor. As a result, new drugs acting on the receptor have been suggested as novel treatments for obesity and diabetes [PMID: 16517404, PMID: 19009545, PMID: 18037923]. Although GPR119 is phylogenetically related to cannabinoid receptors, only fatty acid amides interact with GPR119 [PMID: 16517404, PMID: 15607732, PMID: 17289847, PMID: 21079038]. The potency order is N-oleoyl dopamine > oleoyl ethanolamide > palmitoyl ethanolamide > anandamide [PMID: 16517404, PMID: 19901198]. However, because only N-oleoyl dopamine and oleoyl ethanolamide have reasonably high (low micromolar) affinity for GPR119, and because neither of these lipids interacts with CB1 or CB2 receptors, GPR119 cannot currently be viewed as a cannabinoid receptor [PMID: 21079038].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
  • cd15104 (7tmA_GPR119_R_insulinotropic_r)