To compare cortisol and epinephrine action on oral glucose tolerance, healthy humanswere infused with either cortisol (0.1 mg · kg−1 · h−1), epinephrine (5.4 μg · kg−1 · h−1), or saline before and aftera 75-g glucoseload, thereby elevating the respective plasma hormone concentrations into the pathophysiologic range. In the basal state, epinephrine increased arterial concentrations of glucose, β-hydroxybutyrate, and free fatty acids (FFA) as well as splanchnic output of glucose and β-hydroxybutyrate and splanchnic FFA more than cortisol. Postprandially, C-peptide release and hyperinsulinemia were blunted by epinephrine initially and increased less thereafter than during cortisol infusion. The rise in arterial glucose after glucose ingestion as calculated by the area under the curve was more marked (P < .01) after epinephrine [(1.90 ± 0.08 M)150 min] and cortisol [(1.41 ± 0.05 M)150 min] than in the control study [(1.07 ± 0.04 M)150 min]. In parallel, the stress hormones induced an almost identical 24 and 31% rise in mean splanchnic glucose output versus control values (normal, 44.8 ± 2.5; cortisol, 55.3 ± 3.3; epinephrine, 58.9 ± 6.9 g/150 min). The associated rise in arterial concentrations and splanchnic output of insulin above control values was considerably greater during cortisol but unchanged during epinephrine exposure. Epinephrine but not cortisol induced a rise versus the control study in splanchnic uptake of lactate and FFA, as well as in pyruvate output, whereas plasma β-hydroxybutyrate and acetoacetate remained unchanged. The postprandial splanchnic glucose output-to-splanchnic C-peptide output ratio did not differ from normal during epinephrine but was reduced (P < .01) during cortisol administration. Hepatic insulin uptake was proportionate to insulin production rate, whereas hepatic insulin clearance was unaffected by stress hormone action.
We conclude that besides inhibiting adequate insulin release to hyperglycemia, acute epinephrine exposure induces peripheral insulin resistance and increased splanchnic glucose output and lactate uptake. Such insulin resistance seems to be unveiled by normal but inappropriately low postprandial insulin release during epinephrine-induced basal and postprandial hyperglycemia but is partly disguised by secondary hyperinsulinemia after cortisol infusion.
