α1-Adrenergic receptors increase glucose oxidation under normal and ischemic conditions in adult mouse cardiomyocytes

The role of catecholamine receptors in cardiac energy metabolism is unknown. alpha(1)-adrenergic receptors (alpha(1)-ARs) have been identified to play a role in whole body metabolism but its role in cardiac energy metabolism has not been explored. We used freshly prepared primary adult mouse cardiomyocytes and incubated with either(14)C-palmitate or(14)C-glucose tracers to measure oxidation rates in the presence or absence of phenylephrine, an alpha(1)-AR agonist (with beta and alpha(2)-AR blockers) under normal cell culture conditions.(14)CO(2)released was collected over a 10 min period in covered tissue culture plates using a 1 M hyamine hydroxide solution placed in well cups, counted by scintillation and converted into nmoles/hr. We found that phenylephrine stimulated glucose oxidation but not fatty acid oxidation in adult primary cardiomyocytes. alpha(1)-AR stimulated glucose oxidation was blocked by the AMPK inhibitor, dorsomorphin dihydrochloride, and the PKC inhibitor, rottlerin. Ischemic conditions were induced by lowering the glucose concentration from 22.5 mM to 1.375 mM. Under ischemic conditions, we found that phenylephrine also increased glucose oxidation. We report a direct role of alpha(1)-ARs in regulating glucose oxidation under normal and ischemic conditions that may lead to new therapeutic approaches in treating ischemia.

Automated summary

The study showed that phenylephrine can stimulate glucose oxidation in adult primary cardiomyocytes but not fatty acid oxidation. Additionally, under ischemic conditions, phenylephrine also increased glucose oxidation. This suggests a potential new therapeutic approach in treating ischemia through regulation of glucose oxidation by alpha(1)-ARs.