THE ROLE OF β-ARRESTIN PROTEINS IN CARDIAC ENERGY METABOLISM

Objective: β-arrestins are G-protein coupled receptor (GPCR) signal regulation proteins. These proteins are involved in metabolic or functional effects of agonist and biased agonist ligands. The aim of this study was to evaluate the potential effects of β-arrestins on cardiac substrate metabolism.Material and Method: To eliminate G-protein effects and to focus specifically on the β-arrestin signal, we used carvedilol, a β-arrestin-biased agonist. Changes in glucose and palmitate oxidation after carvedilol administration were assessed in control mouse hearts. Western blotting was used to evaluate the phosphorylation levels of protein kinase B (Akt), extracellular signal-regulated kinase (ERK) and pyruvate dehydrogenase (PDH) proteins in these hearts. Hypertrophy was induced with phenylephrine in H9c2 cells. Glucose metabolism was measured in cells treated with carvedilol or prazosin using insulinated perfusate.Result and Discussion: Carvedilol did not alter glucose or palmitate oxidation rates in control mouse hearts. However acute administration of carvedilol influenced ERK and PDH phosphorylation in the hearts. In hypertrophied H9c2 cells, carvedilol treatment decreased glycolysis and slightly increased glucose oxidation which resulted in a significant amelioration in glycolysis-glucose oxidation coupling. In conclusion, carvedilol and β-arrestins may improve glucose metabolism.