COMPARISON OF THE DIRECT AND INDIRECT EFFECTS OF EPINEPHRINE ON HEPATIC GLUCOSE-PRODUCTION

To determine the extent to which the effect of a physiologic increment in epinephrine (EPI) on glucose production (GP) arises indirectly fro m its action on peripheral tissues (muscle and adipose tissue), epinep hrine was infused intraportally (EPI po) or peripherally (EPI pe) into 18-h-fasted conscious dogs maintained on a pancreatic clamp, Arterial EPI levels in EPI po and EPI pe groups rose from 97+/-29 to 107+/-37 and 42+/-12 to 1,064+/-144 pg/ml, respectively, Hepatic sinusoidal EPI levels in EPI po and EPI pe were indistinguishable (561+/-84 and 568/-75 pg/ml, respectively), During peripheral epinephrine infusion, GP increased from 2.2+/-0.1 to 5.1+/-0.2 mg/kg . min (10 min), In the pre sence of the same rise in sinusoidal EPI, but with no rise in arterial EPI (during portal EPI infusion), GP increased from 2.1+/-0.1 to 3.8/-0.6 mg/kg . min. Peripheral EPI infusion increased the maximal gluco neogenic rate from 0.7+/-0.4 to 1.8+/-0.5 mg/kg . min. Portal EPI infu sion did not change the maximal gluconeogenic rate, The estimated init ial increase in glycogenolysis was approximate to 1.7 and 2.3 mg/kg . min in the EPI pe and EPI po groups, respectively, Gluconeogenesis was responsible for 60% of the overall increase in glucose production sti mulated by the increase in plasma epinephrine (EPI pe), Elevation of s inusoidal EPI per se had no direct gluconeogenic effect on the liver, thus its effect on glucose production was solely attributable to an in crease in glycogenolysis, Lastly, the gluconeogenic effects of EPI mar kedly decreased (60-80%) its overall glycogenolytic action on the live r.