Effect of epinephrine on muscle glycogenolysis and insulin-stimulated muscle glycogen synthesis in humans

To examine the effects of a physiological increase in plasma epinephrine concentration (similar to 800 pg/ml) on muscle glycogenolysis and insulin-stimulated glycogenesis, we infused epinephrine [1.2 mu g . (m(2) body surface)(-1) . min(-1)] for 2 h and monitored muscle glycogen and glucose 6-phosphate (G-6-P) concentrations with C-13/P-31 nuclear magnetic resonance (NMR) spectroscopy. Epinephrine caused an increase in plasma glucose (Delta similar to 50 mg/dl), lactate (Delta similar to 1.4 mM), free fatty acids (Delta similar to 1,200 mu M at peak), and whole body glucose oxidation (Delta similar to 0.85 mg . kg(-1) . min(-1)) compared with levels in a group of control subjects (n = 4) in the presence of slight hyperinsulinemia (similar to 13 mu U/ml, n = 8) or basal insulin (similar to 7 mu U/ml, n = 7). However, epinephrine did not induce any detectable changes in glycogen or G-6-P concentrations, whereas muscle inorganic phosphate (P-i) decreased by 35%. Epinephrine infusion during a euglycemic-hyperinsulinemic clamp (n = 8) caused a 45% decrease in the glucose infusion rate that could be mostly attributed to a 73% decrease in muscle glycogen synthesis rate. After an initial increase to similar to 160% of basal values, G-6-P levels decreased by similar to 30% with initiation of the epinephrine infusion. We conclude that a physiological increase in plasma epinephrine concentration 1) has a negligible effect on muscle glycogenolysis at rest, 2) decreases muscle P-i, which may maintain phosphorylase activity at a low level, and 3) causes a major impairment in insulin-stimulated muscle glycogen synthesis, possibly due to inhibition of glucose transport-phosphorylation activity.