The time course of myocardial glycogenolysis stimulated by glucagon

The rate of glycogenolysis was measured using 13C-NMR in vivo in the rat heart following a glucagon bolus. Glycogen that had just been synthesized during a 50 min infusion of D-[1-13C]glucose and insulin was degraded at a rate of 2.5 mumol/min/g wet wt following a 250 micrograms bolus of glucagon. If a second 50 min infusion of unlabelled glucose followed the D-[-13C]glucose, the rate of mobilization of the labelled glycogen following glucagon was slower (0.52 mumol/min/g wet wt), indicating that the labeled glycogen was less accessible to the activated phosphorylase. Glycogen phosphorylase a (GPa) activity was measured in hearts freeze-clamped at intervals after the glucagon bolus. Activity rose rapidly to 6-fold basal and then returned to basal over 20-30 min (t1/2 decay of phosphorylase activity = 5.1 min). This time course paralleled the exponential fall in heart glycogen which followed glucagon (t1/2 = 4.3 min). Throughout the post-glucagon period the activity of phosphorylase exceeded the rate of glycogenolysis. These findings suggest that the activity of the phosphorylated form of glycogen phosphorylase (GPa) is an important but not the sole determinant of glycogen breakdown in the heart after a glucagon bolus.