Epinephrine-stimulated glucose production is not diminished by starvation: evidence for an effect on gluconeogenesis.

We infused physiological doses of epinephrine (1.2 microgram/m2 X min) into six healthy obese subjects in the postabsorptive state and after 3-4 days of starvation. During starvation, a reduction in hepatic glycogen stores was demonstrated by the absence of a rise in plasma glucose and glucose production (using [3-3H]glucose) in response to glucagon infusion. The increases in plasma epinephrine and glucose during the epinephrine infusion were comparable before and after starvation. Most importantly, the increase in endogenous glucose production produced by epinephrine was virtually unaffected, i.e. the initial rise in glucose production (59% vs. 49%), the incremental area under the curve (2.6 vs. 3.1 g/m2), and the spike-decline pattern of the response were no different before and after starvation, respectively. Similarly, epinephrine-induced elevations in gluconeogenic precursors (lactate and alanine) were not altered by starvation. However, starvation accentuated the rise in FFA by 200%. We conclude that starvation does not diminish the rise in endogenous glucose production in response to stress-like elevations of epinephrine. This occurs even though the liver fails to respond to high physiological doses of glucagon, possibly because epinephrine enhances the mobilization of gluconeogenic precursors and FFA. These data suggest that epinephrine is a potent stimulator of gluconeogenesis and may be more effective than glucagon in accelerating glucose production in patients with depleted glycogen stores.