Nomenclature: GPR119

Family: Class A Orphans

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

This receptor has a proposed ligand; see the Latest Pairings page for more information.

Contents

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 335 Xq26.1 GPR119 G protein-coupled receptor 119 9
Mouse 7 335 X A4 Gpr119 G-protein coupled receptor 119
Rat 7 468 Xq35 Gpr119 G protein-coupled receptor 119
Previous and Unofficial Names
hGPCR2
GPCR2
SNORF25
GPR119
G-protein coupled receptor 119
G-protein coupled receptor 2
glucose-dependent insulinotropic receptor
G protein-coupled receptor 119
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
N-oleoylethanolamide
Comments: Proposed ligand, two publications
Rank order of potency
N-oleoylethanolamide, N-palmitoylethanolamine > SEA (anandamide is ineffective)  [31]
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
compound 8g [PMID:21444206] Hs Agonist 9.3 pEC50 39
pEC50 9.3 (EC50 5x10-10 M) [39]
compound 23 [PMID:21444206] Hs Agonist 9.22 pEC50 39
pEC50 9.22 (EC50 6x10-10 M) [39]
compound 29a [PMID:21444206] Hs Agonist 9.15 pEC50 39
pEC50 9.15 (EC50 7x10-10 M) [39]
compound 3j [PMID:21444206] Hs Agonist 9.05 pEC50 39
pEC50 9.05 (EC50 9x10-10 M) [39]
compound 3a [PMID:21444206] Hs Agonist 8.96 pEC50 39
pEC50 8.96 (EC50 1.1x10-9 M) [39]
5-(4-cyano-3-methylphenyl)-2-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)nicotinitrile Hs Agonist 8.77 pEC50 40
pEC50 8.77 (EC50 1.7x10-9 M) [40]
compound 36j [PMID:21536438] Hs Agonist 8.52 pEC50 48
pEC50 8.52 (EC50 3x10-9 M) [48]
compound 58 [PMID:21273063] Hs Agonist 8.4 pEC50 44
pEC50 8.4 (EC50 4x10-9 M) [44]
AR231453 Hs Agonist 8.2 pEC50 6
pEC50 8.2 [6]
compound 42 [PMID:22545772] Hs Agonist 8.1 pEC50 36
pEC50 8.1 (EC50 8x10-9 M) [36]
compound 20f [PMID:21536438] Hs Agonist 7.74 pEC50 48
pEC50 7.74 (EC50 1.8x10-8 M) [48]
compound 36 [PMID:21273063] Hs Agonist 7.72 pEC50 44
pEC50 7.72 (EC50 1.9x10-8 M) [44]
JNJ-38431055 Hs Agonist 7.3 pEC50 38
pEC50 7.3 [38]
compound 3 [PMID:21310611] Hs Agonist 7.1 pEC50 27
pEC50 7.1 [27]
(R)-N-oleoyltyrosinol Hs Agonist 6.3 pEC50 5
pEC50 6.3 [5]
(S)-N-oleoyltyrosinol Hs Agonist 6.2 pEC50 5
pEC50 6.2 [5]
isopropyl-4-(3-cyano-5-(quinoxalin-6-yl)pyridine-2-yl)piperazine-1-carboxylate Hs Agonist 6.1 pEC50 40
pEC50 6.1 (EC50 7.86x10-7 M) [40]
AS1907417 Hs Agonist 6.0 pEC50 52
pEC50 6.0 [52]
N-oleoylethanolamide Hs Agonist 5.4 – 6.3 pEC50 5,31,42
pEC50 5.4 – 6.3 [5,31,42]
oleoyl-lysophosphatidylcholine Hs Agonist 5.8 pEC50 41
pEC50 5.8 [41]
1-palmitoyl-lysophosphatidylcholine Hs Agonist 5.8 pEC50 41
pEC50 5.8 [41]
AS1535907 Hs Agonist 5.3 – 5.9 pEC50 29,50-51
pEC50 5.3 – 5.9 [29,50-51]
AS1269574 Hs Agonist 5.6 pEC50 49
pEC50 5.6 [49]
1-oleoyl glycerol Hs Agonist 5.6 pEC50 15
pEC50 5.6 [15]
2-oleoyl glycerol Hs Agonist 5.6 pEC50 15
pEC50 5.6 [15]
1-stearoyl-lysophosphatidylcholine Hs Agonist 5.5 pEC50 41
pEC50 5.5 [41]
N-oleoyldopamine Hs Agonist 5.5 pEC50 5
pEC50 5.5 [5]
2-methyl-2-propanyl 1'-(3-pyridinyl)-4,4'-bipiperidine-1-carboxylate Hs Agonist 5.44 pEC50 44
pEC50 5.44 (EC50 3.6x10-6 M) [44]
PSN632408 Hs Agonist 5.3 pEC50 31
pEC50 5.3 [31]
lysophosphatidylethanolamine Hs Agonist 5.2 pEC50 41
pEC50 5.2 [41]
lysophosphatidylinositol Hs Agonist 5.2 pEC50 41
pEC50 5.2 [41]
olvanil Hs Agonist 5.1 pEC50 5
pEC50 5.1 [5]
PSN375963 Hs Agonist 5.1 pEC50 31
pEC50 5.1 [31]
Agonist Comments
Endogenous agonists for GPR119 include lipid compounds. For a review summarising the range of endogenous lipids tested at this receptor and the role of GPR119 as a fat sensor see [14]. In addition to those agonists displayed in the table, 5-hydroxy-eicosapentaenoic acid (5-HEPE) displays agonist activity at mammalian GPR119, with EC50 values ranging from 0.003-3 µM in the human and mouse receptors (the reference does not specify which data is for each species) [21].

A pharmacophore model for GPR119 agonists is described by Zhu et al. [53].

A number of low-affinity synthetic agonists based on the structure of AR231453 are outlined in [37]. Similarly, a range of 2,5-disubstituted pyridines are assessed for their properties as GPR119 agonists in [47].

Treatment with agonists OEA or PSN632408 has been demonstrated to increase intracellular cAMP levels in a HEK-OSGPR116 cell line in a concentration dependent manner [31]. Treatment of GPR119-transfected HEK293 cells with AR231453 caused an increase in intracellular cAMP levels [6]. Additionally, treatment of HIT-T15 cells with AR231453 led to enhanced insulin release [6]. Experiments in mice in the same study showed improved glucose tolerance following treatment with AR231453 in wild-type mice. The same effect was not seen in GPR119-deficient mice. Another study revealed AR231453 when used to treat GLUTag cells causes calcium influx [23].

A review by Lauffer et al. summarises the findings of others to suggest that half of the in vivo agonism of GPR119 is mediated by intestinal L-cells and the other half by pancreatic β-cells [25].

Agonists OEA, PSN375963, PSN632408 and oleoyl-lysophosphatidylcholine all signal through GPR119 selectively although oleoyl-lysophosphatidylcholine also acts through GPR119-independent mechanisms [30]. It has been demonstrated that Gpr119 is not required for the hypophagic action of endogenous ligand oleoylethanolamide as a decreased food intake was seen in both Gpr119+/+ and Gpr119-/- mice when treated with oleoylethanolamide [24]. In high glucose conditions, treatment of mice with AS1269574 stimulated insulin release from β-cells [49].

In 2008, Arena Pharmaceuticals reported GPR119 agonist APD597 has entered Phase 1 clinical trials as a type 2 diabetes candidate. The results of Katz et al. (2011) show novel agonist JNJ-38431055 to have potential as an anti-diabetic therapy [19]. Other drugs reported to have entered clinical trials include MBX-2982, GSK-1292263 and PSN-821 [54]. JNJ-38431055 has performed well when administered in studies on subjects with type 2 diabetes [20].

AS1907417 has been shown to preserve pancreatic β-cell function in addition to controlling glucose levels [52]. The mouse pancreatic β-cell line MIN6-B1 when treated with AS1907417 displayed a concentration dependent increase in glucose-sensitive insulin secretion (GSIS) at high glucose concentrations. The same study showed that chronic treatment of diabetic db/db mice with AS1907417 resulted in increased expression of both pancreatic insulin and PDX-1 genes.

Treatment of GPR119-expressing human COS-7 cells with 2-oleoyl glycerol led to elevated levels of cAMP in the cells and elevated plasma GLP-1 [15]. These results were also seen in in vivo studies where GPR119 agonists were administered to a group of human subjects, whereby plasma concentrations of GLP-1 and GIP increase following 2-oleoyl glycerol treatment.

McClure et al. outline the synthesis of a series of bridged piperidine (oxaazabicyclo) compounds, which display potent agonist and antagonist properties at the receptor. Studies on the conformation of these compounds demonstrated that in the case of compounds 1, 8 and 9 the conformation of the molecule in either equatorial or axial form determines its property to act as either an agonist or antagonist at the receptor [28].

Agonist 5-(4-cyano-3-methylphenyl)-2-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)nicotinitrile (compound 2 in the reference) in addition to high efficacy at the human receptor demonstrated stability in rat plasma [40]. Compound 36, when tested by Xia et al. was found to be active in lowering blood glucose levels in a mouse model and to induce an increase in plasma insulin levels in a rat model of hyperglycaemia [48]. Treatment of db/db mice with AS1535907 for three weeks led to an increase in pancreatic insulin and pancreatic β-cell transcription factors (Nkx 2.2, Nkx 6.1, NeuroD and PC1) required for pancreatic development and endocrine cell differentiation [51].
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
Comments:  Detection of elevated cAMP levels of GRP119-transfected HEK293 cells with high levels of GPR119 expression indicate Gαs -coupled signalling leading in turn to activation of adenylyl cyclase [6,25].
References:  41
Tissue Distribution
Pancreas, GI tract (duodenum, jejunum, ileum, stomach, colon)
Expression level:  High
Species:  Human
Technique:  Taqman analysis, RT-PCR
References:  4
Melanocytes
Species:  Human
Technique:  RT-PCR
References:  35
Pancreas (high), testis, skeletal muscle, small intestine, stomach and heart (low)
Species:  Human
Technique:  RT-PCR
References:  41
Pancreas, with greatest expression in the β cells of the islets
Species:  Mouse
Technique:  Quantitative TaqMan analysis, in situ hybridisation
References:  6
Basal forebrain: medial septal, horizontal and vertical diagonal band nuclei (strong signal); lateral septal nuclei, substantia innominata and the ventral pallidum (moderate signals)
Species:  Mouse
Technique:  Hybridisation
References:  2
Detected in mouse pancreatic cell lines NIT-1 and MIN6
Species:  Mouse
Technique:  RT-PCR
References:  41
Pancreatic polypeptide (PP)-cells of islets
Species:  Mouse
Technique:  Immunohistochemistry and double-immunofluorescence
References:  34
Pancreatic islets (high), intestine (low)
Species:  Mouse
Technique:  RT-PCR
References:  24
K cells
Species:  Mouse
Technique:  RT-PCR
References:  32
Pancreas, colon. Found in high levels in the proximal colon.
Species:  Mouse
Technique:  RNase protection analysis, in situ hybridisation
References:  4
Pancreatic polypeptide (PP)-cells of islets
Species:  Rat
Technique:  Immunohistochemistry and double-immunofluorescence
References:  34
Pancreas, predominantly in β-cell lines and islets
Species:  Rat
Technique:  RT-PCR
References:  41
Tissue Distribution Comments
In the rat pancreas, distribution has been demonstrated to be higher in the islet cells than in the pancreas as a whole [41]. These findings are supported by those of Sakamoto et al. who found gpr119 to be expressed in a mouse MIN6 cell line, detected by Northern blot analysis and confirmed by RT-PCR [34]. Immunofluorescence analysis in rat and mouse also confirmed the expression of GPR119 in β cells in the pancreatic islets [6]. Northern blot analysis of GLUTag, NIT-T15 and STC-1 cells demonstrated labelled mouse GPR119 expression [4]. The same study also found high levels of GPR119 expression in region of mouse colon where modulators of GLP-1 release are particularly effective suggesting colocalisation with other receptors with endocrine function. Preproglucagon-expressing cells in the mouse colon were found to be positive for GPR119 expression.

The study by Lan et al. finding strong expression of GPR119 in mouse pancreatic islets also found strong expression in mouse insulinoma (Min6-C4) cells [24]. GPR119 was detected in K cells expressed in transgenic mice using quantitative RT-PCR [32].

The expression pattern of GPR119 in the GI tract is highly similar to that if PYY-expressing L-cells [7].

Cell line expression analysis with α-TC1-6 cells and STC-1 cells revealed significantly higher levels of expression in the α-TC1-6 cells [46].
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Treatment with agonist AS1535907 caused increased insulin secretion and a transient increase in human insulin promoter activity
Species:  Human
Tissue:  NIT-1 cell line
Response measured:  Insulin secretion, human insulin promotor activity
References:  51
Insulin secretion was shown to be increased in parental RINm5f cells not expressing GPR119 following treatment with GLP-1 and OLPC. This response was not seen with OEA treatment, or with treatment with synthetic agonists for GPR119. In RINm5f cells expressing GPR119, increased insulin secretion was seen following treatment with OEA, OLPC and synthetic agonists PSN275963 and PSN632408
Species:  Rat
Tissue:  RINm5f insulinoma cell line
Response measured:  Insulin secretion
References:  30
siRNA specific to mouse GPR119 was demonstrated to block oleoyl-lysophosphatidylcholine (18.1-LPC)-potentiated insulin secretion from NIT-1 cells
Species:  Mouse
Tissue:  NIT-1 cells
Response measured:  Insulin secretion
References:  41
First-phase insulin secretion is higher in AS1535907-treated rat perfused pancreas than in control-treated groups
Species:  Rat
Tissue:  Pancreas
Response measured:  Insulin secretion
References:  51
A NCI-H716 cell model analysed by RT-PCR and cAMP and GLP-1 radioimmunoassay showed significantly increased GLP-1 secretion from the cells following treatment with oleoylethanolamide. Applying high concentrations of oleoylethanolamide led to a reduced level of GLP-1 release suggesting desensitisation of the cells
Species:  Human
Tissue:  NCI-H716 cell model
Response measured:  GLP-1 secretion
References:  26
Functional Assay Comments
The assay showing insulin secretion following treatment with GR119 agonists demonstrates the selective vs. non-selective activity of the various GPR119 agonists.

The findings of Lauffer et al. showing increased secretion of GLP-1 following treatment with oleoylethanolamide were also seen in a murine GLUTag cells line and rat intestinal L-cell models. Increased cAMP levels were also observed [26].
Physiological Functions
Maintenance of glycaemic control
Species:  Human
Tissue:  Pancreatic insulin-producing -cells and intestinal glucagon-like peptide-1-producing L-cells
References:  5
The distribution of GPR119 in the GI tract and interaction with oleoylethanolamide suggests a role in regulation of satiety
Species:  Rat
Tissue:  Pancreas and GI tract
References:  22
Stimulation of cAMP accumulation and GLP-1 release by GLUTag cells was observed following treatment by GPR119 agonist AR231453. Treatment with this agonist also increased GIP levels in vivo in rats.
Species:  Mouse
Tissue:  GLUTag cells
References:  4
Promotes a decrease in food intake through a strong association with adipose tissue fatty acid amide hydrolase
Species:  Mouse
Tissue:  Adipose tissue
References:  45
Activation of GPR119 inhibits electrolyte secretion in a glucose dependent manner in colon epithelial cells in humans and mice. This effect is mediated by PYY.
Species:  Human
Tissue:  Colon epithelial cells
References:  7
Mediation of incretin release and glucose homeostasis
Species:  Mouse
Tissue:  Intestinal and pancreatic tissue
References:  4
Activation of GPR119 results in stimulation of β-cell replication in pancreatic islets. This effect is accentuated with treatment with a GPR119 agonist.
Species:  Mouse
Tissue:  Pancreatic islets
References:  10
Physiological Functions Comments
GPR119 was first proposed to have a role in mediating insulin secretion via LPC by Soga et al. (2005) [41]. Overton et al. hypothesised that GPR119 plays a hypophagic role given its intestinal localisation and the fact endogenous agonists OEA, PEA, and SEA have been shown in a rat model to reduce feeding behaviour [31]. The proposed role of GPR119 in glucose homeostasis was further supported by the finding that treatment with GPR119 agonist AR231453 resulted in improved glucose tolerance in rats [4]. The dual action of GPR119 agonists leading to incretin secretion and β-cell stimulation demonstrates the two established physiological functions of the receptor [17]. GPR119-mediated secretion of insulin is glucose-dependent whereas secretion of GLP-1 is glucose independent [23].
Physiological Consequences of Altering Gene Expression Comments
There are no consistent abnormalities in the tissues of the Gpr119-/- mice. Similarly, not behavioural differences or significant different were observed in analysis of urine [24]. In investigation of further genotypic differences the same study demonstrated lower body mass in the Gpr119-/- genotype than the Gpr119+/+ genotype when mice were fed with a diet of semi-purified LFD [24]. In a further experiment measuring GLP-1[7-36]amide and total GIP levels in the wild type and knockout mice, a genotypic difference was seen in GLP-1[7-36] levels. Lower levels were seen in the Gpr119-/- following oral glucose load, whereas a three-fold increase was seen in GLP-1[7-36]amide in the Gpr119-/- mice. However, the two genotypes did not display a significant difference in overall GIP levels following glucose load. These results indicate GPR119 signalling is involved in the regulation of GLP-1 secretion following food intake.
Gene Expression and Pathophysiology
There is statistically significant differentiation in the expression pattern of GPR119 between metastases and benign nevi across the three metastatic sites tested
Tissue or cell type:  Subcutis, regional lymph nodes, brain
Pathophysiology:  Metastatic melanoma
Species:  Human
Technique:  Quantitative PCR analysis
References:  33
Gene Expression and Pathophysiology Comments
In obese hyperglycaemic db/db mice, gpr119 mRNA expression levels were elevated in pancreatic islets [34]. This supports GR119 having a role in the pathogenesis of diabetes and obesity.
Biologically Significant Variants
Type:  SNP
Species:  Human
Change:  S309L
Global MAF (%):  <1
Subpopulation MAF (%):  AFR: 1
Minor allele count:  A=0.001/2
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession: 
Validation:  1000 Genomes, HapMap
General Comments
Proposed ligand (oleoylethanolamide), supported by one publication [31]. GPR119 is one of the rhodopsin-type GPCRs [9]. Although not a cannabinoid receptor, GPR119 is a target of the endocannabinoid system [18].

GPR119 represents a potential drug target in the treatment of obesity and diabetes [17,34]. Due to the expression pattern of GPR119, targeting the receptor with agonists may prove to be a better therapeutic strategy than current treatments for diabetes [17]. As of 2008, GPR119 agonists were in clinical trials with focus on their effects both on pancreatic insulin secretion and intestinal GLP-1 release [8].

By 2009 there was some consensus in the literature that OEA was the main endogenous ligand for GPR119 [3].

Phylogenetic studies have assigned GPR119 to the MECA (melanocortin; endothelial differentiation gene; cannabinoid; adenosine) receptor cluster, with cannabinoid receptors as its closest relatives [12].

The highest potency agonist, oleoylethanolamide is one of the acylethanolamides group of compounds. Modulation of the levels of acylethanolamides in the gut has been explored as a strategy for the control and treatment of eating disorders and inflammatory bowel conditions [3]. However, the extent to which GPR119 is involved in the weight-reducing effects of oleoylethanolamide is not yet understood [13].

Mutation studies on GPR119 revealed mutation of the tryptophan residue at position 13 of transmembrane region V1, conserved across GPCRs is essential to the function of the receptor, with all constitutive activity of the receptor eliminated when Trp13 was substituted with Ala [16].

GPR119 is upregulated in response to OEA [45]. However, it has also been shown the cytoprotective effects of OEA are not mediated through GPR119 [43].

Mice with deletion of the glucagon and GLP-1 receptors (Gcgr–/–,Glp1r–/–) display increased expression of gpr119 in pancreatic islets and increased sensitivity to cholecystokinin and GPR119 agonist AR231453 revealing compensatory mechanisms of insulin secretion control and therefore plasticy in the incretin axis and β-cell function [1]. An additional study showed that AR231453 stimulates the proliferation of β-cells and improves the function of pancreatic islet grafts in diabetic mice. These results include increased GLP-1 secretion following AR231453 treatment [11]. The therapeutic implication for this finding is that single-islet as opposed to full pancreatic transplant may be possible, and that GPR119 agonists are successful in restoring normoglycemia. These results are supported by a further study demonstrating that normoglycemia can be achieved more rapidly in diabetic mice treated with GPR119 agonists OEA or PSN632408 than those treated with a vehicle [10]. Both these agonists are shown to stimulate β-cell replication in vitro and in vivo thereby increasing β cell mass and improving graft function.
Available Assays
DiscoveRx PathHunter® eXpress GPR119 HEK 293 β-Arrestin GPCR Assay (Cat no. 93-0356E1CP0M)
PathHunter® HEK 293 GPR119 β-Arrestin Cell Line (Cat no. 93-0356C1)
PathHunter® U2OS GPR119 β-Arrestin Cell Line (Cat no. 93-0356C3)
more info

REFERENCES

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2. Bonini, James A. et al.. (2002) Methods of identifying compounds that bind to SNORF25 receptors. Patent number: US6468756. Assignee: Synaptic. Priority date: 22/02/1999. Publication date: 22/10/2002.

3. Borrelli F, Izzo AA. (2009) Role of acylethanolamides in the gastrointestinal tract with special reference to food intake and energy balance. Best Pract. Res. Clin. Endocrinol. Metab.23 (1): 33-49. [PMID:19285259]

4. Chu ZL, Carroll C, Alfonso J, Gutierrez V, He H, Lucman A, Pedraza M, Mondala H, Gao H, Bagnol D et al.. (2008) A role for intestinal endocrine cell-expressed g protein-coupled receptor 119 in glycemic control by enhancing glucagon-like Peptide-1 and glucose-dependent insulinotropic Peptide release. Endocrinology149 (5): 2038-47. [PMID:18202141]

5. Chu ZL, Carroll C, Chen R, Alfonso J, Gutierrez V, He H, Lucman A, Xing C, Sebring K, Zhou J et al.. (2010) N-oleoyldopamine enhances glucose homeostasis through the activation of GPR119. Mol. Endocrinol.24 (1): 161-70. [PMID:19901198]

6. Chu ZL, Jones RM, He H, Carroll C, Gutierrez V, Lucman A, Moloney M, Gao H, Mondala H, Bagnol D et al.. (2007) A role for beta-cell-expressed G protein-coupled receptor 119 in glycemic control by enhancing glucose-dependent insulin release. Endocrinology148 (6): 2601-9. [PMID:17289847]

7. Cox HM, Tough IR, Woolston AM, Zhang L, Nguyen AD, Sainsbury A, Herzog H. (2010) Peptide YY is critical for acylethanolamine receptor Gpr119-induced activation of gastrointestinal mucosal responses. Cell Metab.11 (6): 532-42. [PMID:20519124]

8. Engelstoft MS, Egerod KL, Holst B, Schwartz TW. (2008) A gut feeling for obesity: 7TM sensors on enteroendocrine cells. Cell Metab.8 (6): 447-9. [PMID:19041758]

9. Fredriksson R, Höglund PJ, Gloriam DE, Lagerström MC, Schiöth HB. (2003) Seven evolutionarily conserved human rhodopsin G protein-coupled receptors lacking close relatives. FEBS Lett.554 (3): 381-8. [PMID:14623098]

10. Gao J, Tian L, Weng G, Bhagroo NV, Sorenson RL, O'Brien TD, Luo J, Guo Z. (2011) Stimulating beta cell replication and improving islet graft function by GPR119 agonists. Transpl. Int.24 (11): 1124-34. [PMID:21902730]

11. Gao J, Tian L, Weng G, O'Brien TD, Luo J, Guo Z. (2011) Stimulating β-cell replication and improving islet graft function by AR231453, A gpr119 agonist. Transplant. Proc.43 (9): 3217-20. [PMID:22099761]

12. Godlewski G, Offertáler L, Wagner JA, Kunos G. (2009) Receptors for acylethanolamides-GPR55 and GPR119. Prostaglandins Other Lipid Mediat.89 (3-4): 105-11. [PMID:19615459]

13. Hansen HS, Diep TA. (2009) N-acylethanolamines, anandamide and food intake. Biochem. Pharmacol.78 (6): 553-60. [PMID:19413995]

14. Hansen HS, Rosenkilde MM, Holst JJ, Schwartz TW. (2012) GPR119 as a fat sensor. Trends Pharmacol. Sci.33 (7): 374-81. [PMID:22560300]

15. Hansen KB, Rosenkilde MM, Knop FK, Wellner N, Diep TA, Rehfeld JF, Andersen UB, Holst JJ, Hansen HS. (2011) 2-Oleoyl glycerol is a GPR119 agonist and signals GLP-1 release in humans. J. Clin. Endocrinol. Metab.96 (9): E1409-17. [PMID:21778222]

16. Holst B, Nygaard R, Valentin-Hansen L, Bach A, Engelstoft MS, Petersen PS, Frimurer TM, Schwartz TW. (2010) A conserved aromatic lock for the tryptophan rotameric switch in TM-VI of seven-transmembrane receptors. J. Biol. Chem.285 (6): 3973-85. [PMID:19920139]

17. Hughes TE. (2009) Emerging therapies for metabolic diseases--the focus is on diabetes and obesity. Curr Opin Chem Biol13 (3): 332-7. [PMID:19482541]

18. Izzo AA, Sharkey KA. (2010) Cannabinoids and the gut: new developments and emerging concepts. Pharmacol. Ther.126 (1): 21-38. [PMID:20117132]

19. Katz LB, Gambale JJ, Rothenberg PL, Vanapalli SR, Vaccaro N, Xi L, Polidori DC, Vets E, Sarich TC, Stein PP. (2011) Pharmacokinetics, pharmacodynamics, safety, and tolerability of JNJ-38431055, a novel GPR119 receptor agonist and potential antidiabetes agent, in healthy male subjects. Clin. Pharmacol. Ther.90 (5): 685-92. [PMID:21975348]

20. Katz LB, Gambale JJ, Rothenberg PL, Vanapalli SR, Vaccaro N, Xi L, Sarich TC, Stein PP. (2012) Effects of JNJ-38431055, a novel GPR119 receptor agonist, in randomized, double-blind, placebo-controlled studies in subjects with type 2 diabetes. Diabetes Obes Metab14 (8): 709-16. [PMID:22340428]

21. Kogure R, Toyama K, Hiyamuta S, Kojima I, Takeda S. (2011) 5-Hydroxy-eicosapentaenoic acid is an endogenous GPR119 agonist and enhances glucose-dependent insulin secretion. Biochem. Biophys. Res. Commun.416 (1-2): 58-63. [PMID:22079287]

22. Lambert DM, Muccioli GG. (2007) Endocannabinoids and related N-acylethanolamines in the control of appetite and energy metabolism: emergence of new molecular players. Curr Opin Clin Nutr Metab Care10 (6): 735-44. [PMID:18089956]

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To cite this database page, please use the following:

Anthony P. Davenport, Stephen Alexander, Joanna L. Sharman, Adam J. Pawson, Helen E. Benson, Amy E. Monaghan, Wen Chiy Liew, Chido Mpamhanga, Jim Battey, Richard V. Benya, Robert T. Jensen, Sadashiva Karnik, Evi Kostenis, Eliot Spindel, Laura Storjohann, Kalyan Tirupula, Tom I. Bonner, Richard Neubig, Jean-Philippe Pin, Michael Spedding, Anthony Harmar.
Class A Orphans: GPR119. Last modified on 09/07/2013. Accessed on 25/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=126.

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