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

Abstract

To examine the effects of a physiological increase in plasma epinephrine concentration (∼800 pg/ml) on muscle glycogenolysis and insulin-stimulated glycogenesis, we infused epinephrine [1.2 μg ⋅ (m2 body surface)−1 ⋅ min−1] for 2 h and monitored muscle glycogen and glucose 6-phosphate (G-6- P) concentrations with13C/31P nuclear magnetic resonance (NMR) spectroscopy. Epinephrine caused an increase in plasma glucose (Δ ∼50 mg/dl), lactate (Δ ∼1.4 mM), free fatty acids (Δ ∼1,200 μM at peak), and whole body glucose oxidation (Δ ∼0.85 mg ⋅ kg−1 ⋅ min−1) compared with levels in a group of control subjects ( n = 4) in the presence of slight hyperinsulinemia (∼13 μU/ml, n = 8) or basal insulin (∼7 μU/ml, n = 7). However, epinephrine did not induce any detectable changes in glycogen or G-6- P concentrations, whereas muscle inorganic phosphate (Pi) 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 ∼160% of basal values, G-6- Plevels decreased by ∼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 Pi, 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.