The effects of epinephrine on ketogenesis in the dog after a prolonged fast

Abstract

The effects of a selective increase in epinephrine on ketogenesis and lipolysis were determined in the conscious dog following a prolonged fast (7 days). Plasma insulin and glucagon were fixed at basal levels by infusion of somatostatin (0.8 μg/kg/min) and basal intraportal replacement amounts of insulin (210 ± 20 μU/kg/min) and glucagon (0.65 ng/kg/min). Following a 40-minute control period, saline or epinephrine (0.04 μg/kg/min) was infused for 3 hours. Plasma insulin, glucagon, and norepinephrine levels did not change during saline (6 ± 1 μU/mL, 83 ± 17 pg/mL, and 137 ± 38 pg/mL, respectively) or epinephrine (10 ± 1 μU/mL, 73 ± 18 pg/ml, 98 ± 13 pg/mL, respectively) infusion. Plasma epinephrine levels increased from 80 ± 26 to 440 ± 47 pg/mL in response to infusion of the catecholamine, but remained unchanged during saline infusion. Glycerol levels (93 ± 10 μmol/L) remained unchanged during saline infusion, but increased in response to epinephrine (108 ± 9 to 170 ± 18 μmol/L by 30 minutes). The glycerol level had returned to baseline and to the value apparent in saline controls by 60 minutes. The nonesterified fatty acid (NEFA) level declined slowly during the 3-hour saline infusion, but was elevated in response to epinephrine infusion (1.27 ± 0.16 to 1.97 ± 0.25 mmol/L at 30 minutes). After the initial epinephrine-induced increase, the NEFA level declined so that by 3 hours it was not significantly different from the basal or saline values. Saline infusion was associated with a decline in ketone body levels and net hepatic ketone production (335 ± 43 to 239 ± 72 μmol/L and 10.99 ± 1.43 to 5.50 ± 1.81 μmol/kg/min). Epinephrine infusion caused an increase in the level and rate of ketone body production, which, when compared with the response in saline-infused animals, was significant at 60, 90, and 120 minutes. While saline infusion had no effect on plasma glucose (95 ± 3 to 89 ± 4 mg/dL) or blood lactate (0.89 ± 0.08 to 0.98 ± 0.19 mmol/L), epinephrine infusion caused both glucose (90 ± 4 to 130 ± 8 mg/dL) and lactate (0.60 ± 0.04 to 1.08 ± 0.17 mmol/L) to increase significantly. These data indicate that, contrary to observations in the 18 hour-fasted dog in which epinephrine had an inhibitory effect on ketogenesis, in a more prolonged fasted dog the catecholamine causes a stimulation of the process.