Metabolic effects of glucagon in the perfused rat heart

Abstract

The effect of glucagon on glycogenolysis and the utilization of acetate-2-C¹⁴ and glucose-U-C¹⁴ was studied in the isolated perfused rat heart. Significant effects of glucagon were obtained with a concentration of 5 µg/ml. Glucagon increased the uptake and oxidation to CO₂ of glucose-U-C¹⁴ and acetate-2-C¹⁴ by 300 and 50%, respectively. The cardiac glycogen content fell to 60% of initial levels in 5 min and then remained constant. Lactate production reached a peak 30 sec after perfusion with glucagon, reflecting the early rapid glycogenolysis, and then fell to a constant rate within 5 min. Steady-state levels of hexose or triose phosphates were increased 300% at a time when glycogen levels had reached a plateau, indicating an increased rate of glucose phosphorylation, after the initial phase of rapid glycogenolysis, despite elevated levels of glucose 6-phosphate. Glucose transport was stimulated by glucagon although glucose entry remained the rate-limiting step of glucose uptake since no free intracellular glucose was detected. The increased fuel utilization produced by glucagon is shown to be dissociated from the glycogenolytic effect and is probably a consequence of the increased work of the heart. The effects of glucagon on the perfused rat heart are identical to those of epinephrine.