GPR119
Identifiers
Aliases	GPR119, GPCR2, G protein-coupled receptor 119
External IDs	OMIM: 300513 MGI: 2668412 HomoloGene: 18670 GeneCards: GPR119
Gene location (Human) Chr. X chromosome (human)[1] Band Xq26.1 Start 130,379,449 bp[1] End 130,385,674 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X|X A5 Start 47,756,856 bp[2] End 47,763,355 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in islet of Langerhans duodenum rectum body of pancreas fundus colon reproductive system reproductive organ male reproductive system gonad Top expressed in islet of Langerhans ileum colon More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity signal transducer activity phosphatidylcholine binding lipid binding Cellular component integral component of membrane receptor complex plasma membrane membrane Biological process G protein-coupled receptor signaling pathway insulin secretion signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 139760 236781 Ensembl ENSG00000147262 ENSMUSG00000051209 UniProt Q8TDV5 Q7TQP3 RefSeq (mRNA) NM_178471 NM_181751 RefSeq (protein) NP_848566 NP_861416 Location (UCSC) Chr X: 130.38 – 130.39 Mb Chr X: 47.76 – 47.76 Mb PubMed search [3] [4]
Wikidata
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G protein-coupled receptor 119 also known as GPR119 is a G protein-coupled receptor that in humans is encoded by the GPR119 gene.^[5]

GPR119, along with GPR55 and GPR18, have been implicated as novel cannabinoid receptors.^[6][7][8]

Pharmacology

GPR119 is expressed predominantly in the pancreas and gastrointestinal tract in rodents and humans, as well as in the brain in rodents.^[9] Activation of the receptor has been shown to cause a reduction in food intake and body weight gain in rats.^[9] GPR119 has also been shown to regulate incretin and insulin hormone secretion.^[10][11][12] As a result, new drugs acting on the receptor have been suggested as novel treatments for obesity and diabetes.^[9][11][13]

Ligands

A number of endogenous, synthetic and plant derived ligands for this receptor have been identified:^[14][15][16]

• 2-Oleoylglycerol (2OG)^[17]
• Anandamide^[13]
• AR-231,453^[18]
• MBX-2982^[19]
• Oleoylethanolamide (OEA)^[6][9][13] (Endogenous Ligand) ^[6]
• PSN-375,963^[9][10]
• PSN-632,408^[9][10]

Human microbiota and GPR119 activation

Commensal bacteria are found to have important roles in human health, as bacterial metabolites are likely to be key components of host interactions by which they affect mammalian physiology.^[20] N-acyl amide synthase genes are found enriched in gastrointestinal bacteria and the lipids, that they encode, interact with GPCRs, which regulate gastrointestinal tract physiology, where cell-based models have demonstrated, that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands, and the clearest overlap in structure and function between bacterial and human GPCR-active ligands, is found for the endocannabinoid receptor GPR119.^[21]

The experiment have isolated both the palmitoyl and oleoyl analogs of N-acyl serinol, and found the latter only differs from 2-OG: C₂₁H₄₀O₄ by the presence of an amide instead of an ester, and from OEA: C₂₀H₃₉NO₂ by the presence of an additional ethanol substituent, where the N-oleoyl serinol (C₂₁H₄₁NO₃; 18:1,n-9),^[22] is a similarly potent GPR119 agonist compared to the endogenous ligand OEA (EC50 12 µM vs. 7 µM), but elicits almost a 2-fold greater maximum activation, do suggest that chemical mimicry of eukaryotic signalling molecules may be common among commensal bacteria,^[21] that communicate through interactions between these two fundamental systems—which form the gut microbiota-endocannabinoidome axis.^[20]

Evolution

References

Further reading