Effect of sequential infusions of glucagon and epinephrine on glucose turnover in the dog.

Conscious dogs were infused with 1) glucagon (3 ng/kg.min) alone for 120 min followed by glucagon plus epinephrine (0.1 microgram/kg.min) for 60 min and 2) epinephrine alone (150 min) followed by epinephrine plus glucagon for 90 min. Glucagon alone caused a 10--15 mg/dl rise in plasma glucose and a 45% increase in glucose production that returned to baseline by 75--120 min. After addition of epinephrine, glucose production rose again by 80%. Infusion of epinephrine alone resulted in unchanged plasma glucagon levels, a 60--70 mg/dl rise in plasma glucose, and an 80--100% rise in glucose production that returned to baseline by 60--120 min. When glucagon was added, glucose output promptly rose again by 85%. When glucagon was infused alone, there was a rise in glucose uptake, whereas, with epinephrine, glucose uptake failed to rise and glucose clearance fell by 35--50%. We conclude that 1) hepatic refractoriness to persistent elevations of glucagon or epinephrine is specific for the hormone infused; 2) epinephrine stimulates glucose production in the conscious dog in the absence of a rise in plasma glucagon; 3) the hyperglycemic response to glucagon or epinephrine is determined in part by accompanying changes in glucose utilization.