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

Abstract

The role of catecholamine receptors in cardiac energy metabolism is unknown. α₁-adrenergic receptors (α₁-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 ¹⁴C-palmitate or ¹⁴C-glucose tracers to measure oxidation rates in the presence or absence of phenylephrine, an α₁-AR agonist (with β and α₂-AR blockers) under normal cell culture conditions. ¹⁴CO₂ 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. α₁-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 α₁-ARs in regulating glucose oxidation under normal and ischemic conditions that may lead to new therapeutic approaches in treating ischemia.

Keywords:

• Glucose
• oxidation
• metabolism
• alpha1-adrenergic
• G-protein coupled receptor

Acknowledgements

We thank Satish Kalhan, MD for his expertise and help in establishing the oxidation assays.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was funded through a grant by the American Heart Association [15GRNT24800004].