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• W2150927388 endingPage "1985" @default.
• W2150927388 startingPage "1978" @default.
• W2150927388 abstract "In type 2 diabetes, impaired insulin-induced Akt/endothelial nitric oxide synthase (eNOS) signaling may decrease the vascular relaxation response. Previously, we reported that this response was negatively regulated by G protein-coupled receptor kinase 2 (GRK2). In this study, we investigated whether/how in aortas from ob/ob mice (a model of type 2 diabetes) GRK2 and β-arrestin 2 might regulate insulin-induced signaling. Endothelium-dependent relaxation was measured in aortic strips. GRK2, β-arrestin 2, and Akt/eNOS signaling pathway proteins and activities were mainly assayed by Western blotting. In ob/ob (vs. control [Lean]) aortas: 1) insulin-induced relaxation was reduced, and this deficit was prevented by GRK2 inhibitor, anti-GRK2 antibody, and an siRNA specifically targeting GRK2. The Lean aorta relaxation response was reduced to the ob/ob level by pretreatment with an siRNA targeting β-arrestin 2. 2) Insulin-stimulated Akt and eNOS phosphorylations were decreased. 3) GRK2 expression in membranes was elevated, and, upon insulin stimulation, this expression was further increased, but β-arrestin 2 was decreased. In ob/ob aortic membranes under insulin stimulation, the phosphorylations of Akt and eNOS were augmented by GRK2 inhibitor. In mouse aorta, GRK2 may be, upon translocation, a key negative regulator of insulin responsiveness and an important regulator of the β-arrestin 2/Akt/eNOS signaling, which is implicated in diabetic endothelial dysfunction." @default.
• W2150927388 created "2016-06-24" @default.
• W2150927388 creator A5012441260 @default.
• W2150927388 creator A5016159315 @default.
• W2150927388 creator A5038613022 @default.
• W2150927388 creator A5068759452 @default.
• W2150927388 date "2012-07-17" @default.
• W2150927388 modified "2023-10-17" @default.
• W2150927388 title "G Protein–Coupled Receptor Kinase 2, With β-Arrestin 2, Impairs Insulin-Induced Akt/Endothelial Nitric Oxide Synthase Signaling in <i>ob/ob</i> Mouse Aorta" @default.
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• W2150927388 doi "https://doi.org/10.2337/db11-1729" @default.
• W2150927388 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3402304" @default.
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• W2150927388 hasPublicationYear "2012" @default.
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