Effect of epinephrine and somatostatin-induced insulin deficiency on ketone body kinetics and lipolysis in man.

Abstract

The effect of elevated plasma epinephrine concentrations (approximately equal to 800 pg/ml) on ketone body kinetics was determined in postabsorptive normal subjects using primed-continuous infusions of 3-14C-acetoacetate. Infusion of epinephrine (60 ng/kg/min) resulted in a transient increase in total ketone body production to a maximum of 2.5-fold the basal rate within 45 min (P less than 0.01 versus controls). Ketone body uptake increased with a delay, compared with production, causing a 2.8-fold increase in total ketone body concentrations (P less than 0.05 versus controls). Plasma free fatty acid (FFA) and blood glycerol concentrations increased transiently during epinephrine; their course was similar to that of ketone body production. Epinephrine administration resulted in hyperglycemia, hyperlactatemia, and a modest increase in plasma insulin and glucagon concentrations. To assess epinephrine's effect on ketone body kinetics during lack of insulin, and to avoid epinephrine-induced alterations in plasma insulin and glucagon concentrations, epinephrine was also infused combined with somatostatin (6.5 micrograms/kg/h). During somatostatin infusion, epinephrine administration resulted in an enhanced and sustained elevation of total ketone body production from 4.4 +/- 0.8 to 15.1 +/- 1.2 mumol/kg/min (P less than 0.01 versus somatostatin alone). Ketone body concentrations increased markedly from 310 +/- 63 to 1763 +/- 137 mumol/L (P less than 0.01 versus somatostatin alone); the ketonemic effect was enhanced due to a 40% decrease of the metabolic clearance rate associated with somatostatin infusion. The increase in plasma FFA and blood glycerol concentrations during somatostatin-induced insulin deficiency was transiently enhanced by epinephrine, such that they increased to 3.2- and 5.6-fold their basal values after 45 min, respectively (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)