GPR119 is expressed predominantly in thepancreas andgastrointestinal tract in rodents and humans, as well as in thebrain 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 regulateincretin andinsulinhormone secretion.[10][11][12] As a result, new drugs acting on the receptor have been suggested as novel treatments forobesity anddiabetes.[9][11][13]
Commensal bacteria are found to have important roles in human health, as bacterialmetabolites are likely to be key components of host interactions by which they affectmammalianphysiology.[20]N-acyl amidesynthase genes are found enriched ingastrointestinalbacteria and thelipids, that they encode, interact withGPCRs, which regulate gastrointestinal tract physiology, where cell-based models have demonstrated, that commensal GPR119 agonists regulate metabolic hormones andglucose 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 thepalmitoyl andoleoyl analogs ofN-acylserinol, and found the latter only differs from 2-OG: C21H40O4 by the presence of anamide instead of anester, and from OEA: C20H39NO2 by the presence of an additionalethanol substituent, where theN-oleoyl serinol (C21H41NO3; 18:1,n-9),[22] is a similarly potent GPR119 agonist compared to the endogenous ligand OEA (EC50 12 μMvs. 7 μM), but elicits almost a 2-fold greater maximum activation, do suggest that chemical mimicry ofeukaryoticsignalling molecules may be common among commensal bacteria,[21] that communicate through interactions between these two fundamental systems—which form thegut microbiota-endocannabinoidomeaxis.[20]
^Izzo AA, Sharkey KA (April 2010). "Cannabinoids and the gut: new developments and emerging concepts".Pharmacology & Therapeutics.126 (1):21–38.doi:10.1016/j.pharmthera.2009.12.005.PMID20117132.
^Shah U (July 2009). "GPR119 agonists: a promising new approach for the treatment of type 2 diabetes and related metabolic disorders".Current Opinion in Drug Discovery & Development.12 (4):519–532.PMID19562648.
^Semple G, Fioravanti B, Pereira G, Calderon I, Uy J, Choi K, et al. (September 2008). "Discovery of the first potent and orally efficacious agonist of the orphan G-protein coupled receptor 119".Journal of Medicinal Chemistry.51 (17):5172–5175.doi:10.1021/jm8006867.PMID18698756.
^Jones RM, Leonard JN, Buzard DJ, Lehmann J (October 2009). "GPR119 agonists for the treatment of type 2 diabetes".Expert Opinion on Therapeutic Patents.19 (10):1339–1359.doi:10.1517/13543770903153878.PMID19780700.S2CID33083682.
Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S (June 2002). "Identification of G protein-coupled receptor genes from the human genome sequence".FEBS Letters.520 (1–3):97–101.doi:10.1016/S0014-5793(02)02775-8.PMID12044878.S2CID7116392.
