Regulation of Ketogenesis by Epinephrine and Norepinephrine in the Overnight-fasted, Conscious Dog

The effects on ketogenesis and lipolysis of a norepinephrine (0.04 μg/kg-min), epinephrine (0.04 μg/kg-min), or saline infusion were examined in the overnight-fasted, conscious dog. Plasma insulin and glucagon levels were maintained constant by means of a somatostatin infusion (0.8 μg/kg-min) and intraportal replacement infusions of insulin and glucagon. In saline-infused dogs, plasma epinephrine (62 ± 8 pg/ml), norepinephrine (92 ± 29 pg/ml), blood glycerol (87 ± 10μM), and plasma nonesterified fatty acid (NEFA) (0.82 ± 0.17 mM) levels did not change. Total blood ketone body levels tended to rise (62 ± 10 to 83 ± 11 μM) by 3 h as did total ketone body production (1.5 ± 0.4 to 2.2 ± 0.4 (μmol/kg-min) over the same time interval. Norepinephrine infusion to produce plasma levels of 447 ± 86 pg/ml caused a sustained 50% rise in glycerol levels (66 ± 17 to 99 ± 15 μmol/L, P < 0.05) and 53% rise in nonesterified fatty acids (0.53 ± 0.07 to 0.81 ± 0.15 μmol/L, P < 0.05). Total ketone body levels rose by 43% (51 ± 8 to 73 ± 10 μmol/L) and ketone body production rose by a similar proportion (1.5 ± 0.2 to 2.2 ± 0.3 μmol/kg-min), changes that did not differ significantly from control animals. A similar increment in plasma epinephrine levels (75 ± 15 to 475 ± 60 pg/ml) caused glycerol levels to rise by 82% (105 ± 23 to 191 ± 26 (μmol/L) in 30 min, but this rise was not sustained and the level fell to 146 ± 14 (μmol/L by 120 min. Plasma nonesterified fatty acids rose from a basal value of 0.89 ± 0.19 mM to 1.25 ± 0.29 mM during the first 30 min, but fell to 0.60 ± 0.12 mM by 2 h. Ketone body levels remained unchanged (66 ± 10 μmol/L) and ketone body production declined (1.5 ± 0.3 to 1.0 ± 0.2 μmol/kgmin). These data indicate that (1) although the sustained increase in lipolysis caused by norepinephrine was greater than that caused by fasting alone, the ketogenic responses were not different, and (2) epinephrine has a transient lipolytic effect and an antiketogenic effect compared with controls.