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Describe novel small-molecule GPR119 agonists with high receptor selectivity and capacity to induce glucose-stimulated insulin (show INS Proteins) secretion.
The GPR119 agonist, HD0471042 increased intracellular cAMP levels in stably human GPR119 expressing CHO cells.
Oxidized-LDL significantly induces lincRNA-DYNLRB2-2 expression, which promotes ABCA1-mediated cholesterol efflux and inhibits inflammation through GPR119 in THP-1 cells.
Replacement of the three methyl groups in 1 with metabolically stable moieties led to the identification of compound 34, a potent and efficacious GPR119 agonist with improved pharmacokinetic (PK) properties.
transfection of GLUTag cells with recombinant human GPR119 results in a constitutive and apparently ligand-independent increase of proglucagon (show GCG Proteins) gene promoter activity and proglucagon (show GCG Proteins) mRNA content.
Results provide evidence of an islet-gastrointestinal distribution of GPR119, its expression in pancreatic beta and alpha cells, and its possible involvement in islet function.
Data suggest that GPR119 activation/up-regulation in skeletal muscle impairs fatty acid and glucose oxidation; diet-induced obesity appears to up-regulate skeletal muscle GPR119.
Data show that Phe-V:13 can serve as an aromatic lock for the proposed active conformation of the Trp (show TBPL1 Proteins)-VI:13 rotameric switch, being involved in the global movement of TM-V and TM-VI in 7TM receptor (show CHRM2 Proteins) activation.
findings show that N-oleoyldopamine (OLDA)& structurally related hydroxybenzyl amides are robust activators of GPR119; studies indicate that multiple, distinct classes of lipid amides, acting via GPR119, may be important modulators of glucose homeostasis
GPR119 therefore represents a novel and attractive potential target for the therapy of obesity and related metabolic disorders.
fat-derived monoacylglycerols are potent candidates for mediating fat-induced GLP-1 (show GCG Proteins) release through GPR119 in vivo.
GPR119 in L-cells plays a key role in oral lipid-triggered GLP-1 (show GCG Proteins) secretion.
Data indicate that G-protein coupled receptor 119 (GPR119) knockout prevents the therapeutic effects of Gordonoside F.
Novel GPR119 agonist, HD0471042, effectively controlled glucose levels and prevented weight gain in type 2 diabetic mice.
AR231453, a GPR119 agonist, can stimulate beta-cell replication and improve islet graft function
Our results demonstrate that combining a GPR119 agonist with a DPP-IV (show DPP4 Proteins) inhibitor may offer a novel therapeutic strategy for stimulating beta-cell regeneration and reversing diabetes.
Data suggest that, in lean mice, 2-oleoylglycerol and linoleylethanolamine serve as physiologically relevant endogenous GPR119 agonists that mediate receptor activation upon nutrient uptake.
GPR119 engages multiple complementary pathways for control of glucose homeostasis.
This gene encodes a member of the rhodopsin subfamily of G-protein-coupled receptors that is expressed in the pancreas and gastrointestinal tract. The encoded protein is activated by lipid amides including lysophosphatidylcholine and oleoylethanolamide and may be involved in glucose homeostasis. This protein is a potential drug target in the treatment of type 2 diabetes.
G protein-coupled receptor 119
, G-protein coupled receptor 2
, glucose-dependent insulinotropic receptor
, G-protein coupled receptor 119