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| http://purl.uniprot.org/citations/26234354 | http://www.w3.org/2000/01/rdf-schema#comment | "A decrease in nitric oxide (NO) production may induce pathological conditions associated with endothelial dysfunction and diabetes. Although a decrease in NO production caused by impaired Akt/endothelial nitric oxide synthesis (eNOS) signaling has been demonstrated at the aorta in the presence of diabetic vascular complications, little is known regarding the details of the mechanism. We identified G-protein-coupled receptor kinase 2 (GRK2) as a critical factor in diabetic endothelial dysfunction. GRK2 plays a role in many physiological functions including regulation of G-protein-coupled receptors (GPCRs). We found that the vasculature affected by type 2 diabetes expresses high levels of GRK2, which may induce endothelial dysfunction caused by impaired Akt/eNOS signaling. GRK2 activation also induces changes in the subcellular localization of GRK2 and β-arrestin 2, a downstream protein, from the cytosol to membrane. In mouse aorta GRK2 may be, on translocation, a key negative regulator and an important regulator of β-arrestin 2/Akt/eNOS signaling, which has been implicated in diabetic endothelial dysfunction. Furthermore, in the aortic membrane of type 2 diabetic model mice under insulin stimulation, the impaired Akt/eNOS signaling was improved by a selective GRK2 inhibitor. These results suggest that in diabetes the GRK2 inhibitor ameliorates vascular endothelial dysfunction via Akt/eNOS signaling by inhibiting GRK2 activity and enhancing β-arrestin 2 translocation to the membrane under GPCR or non-GPCR stimulation, thereby contributing to blood pressure- and blood glucose-lowering effects. We propose that the GRK2 inhibitor may be a promising therapeutic target for cardiovascular complications in type 2 diabetes."xsd:string |
| http://purl.uniprot.org/citations/26234354 | http://purl.org/dc/terms/identifier | "doi:10.1248/yakushi.15-00119"xsd:string |
| http://purl.uniprot.org/citations/26234354 | http://purl.uniprot.org/core/author | "Taguchi K."xsd:string |
| http://purl.uniprot.org/citations/26234354 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26234354 | http://purl.uniprot.org/core/name | "Yakugaku Zasshi"xsd:string |
| http://purl.uniprot.org/citations/26234354 | http://purl.uniprot.org/core/pages | "961-967"xsd:string |
| http://purl.uniprot.org/citations/26234354 | http://purl.uniprot.org/core/title | "[The Role of GRK2 and Its Potential as a New Therapeutic Target in Diabetic Vascular Complications]."xsd:string |
| http://purl.uniprot.org/citations/26234354 | http://purl.uniprot.org/core/volume | "135"xsd:string |
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