It has been suggested that the effects of epinephrine on glucose production by the liver may be mediated through glucagon. To investigate this possibility, epinephrine (EPI) (0.2 or 0.1 μg/kg-min) was infused in 12 conscious normal dogs with or without somatostatin (ST) (0.05 μg/kg-min), a known inhibitor of glucagon and insulin release. EPI (0.2 μg/kg-min) induced a sustained hyperglycemia. This resulted from both an increase in glucose production, which rose initially to 45% above basal and then plateaued at suprabasal levels, and a small but noticeable reduction (18%) in the metabolic clearance rate of glucose. Plasma levels of both immunoreactive glucagon (IRG) and insulin (IRI) also increased transiently. ST plus EPI resulted in a more severe hyperglycemia, which was due to an exaggerated initial peak of glucose production. This response occurred despite a clear suppression (71%) of IRG below basal. ST blunted the initial EPI-induced IRI peak, but IRI never fell below basal with the combined infusion of EPI and ST. The blunting of this initial insulin peak may have affected the hyperglycemie response to EPI. The lower dose of EPI (0.1 μg/kg-min) had a similar but less definite effect on glucose regulation and caused both insulin and glucagon levels to rise. However, at the lower EPI dose, ST had no appreciable effect on insulin release (as judged by peripheral IRI levels), although IRG was again greatly suppressed. Neither the EPI-induced hyperglycemia nor the rapid rise in glucose production was affected by ST, suggesting that the EPI-induced hyperglycemia is not mediated through glucagon release. It also appears that elevated EPI levels can compensate for the role of basal glucagon in regulation of basal glucose production in the postabsorptive state. EPI induced a transient 120% rise in free fatty acid (FFA) levels. The rise in FFA was more marked and more sustained when ST was given together with EPI irrespective of whether the initial EPI-induced insulin peak was blunted or remained unaltered, thus indicating a possible effect of ST on EPI-induced lipoly-sis. The same low dose of ST (0.5 μg/kg-min) infused without EPI greatly suppressed both IRG and IRI below basal (60%).
Thus (1) EPI infusion induced sustained hyperglycemia, resulting from a transient increase in glucose production and an inhibition of metabolic clearance of glucose; both IRG and IRI were also transiently increased. (2) The effect of EPI on glucose production was independent of glucagon, but it was possibly enhanced by suppression of the initial insulin peak. (3) A low dose of ST, which, by itself, suppressed basal IRI and IRG release, was able to override the effect of EPI on IRG but not on IRI release. Thus, the effect of a selective glucagon suppression could be studied. (4) EPI increased plasma FFA only transiently. (5) ST may directly or indirectly increase the lipolytic effect of EPI.