The roles of catecholamines in glucoregulation in intense exercise as defined by the islet cell clamp technique

Exercise at >85% V̇O(2max) causes the greatest known physiological increases in glucose production rates (R(a)). To define the relative roles of catecholamine versus glucagon/insulin responses in stimulating R(a), normal subjects in the postabsorptive state exercised at 87 ± 2% V̇O(2max) during an islet cell clamp (IC): intravenous octreotide (somatostatin analog), 30 ng · kg^-1 · min^-1; glucagon, 0.8 ng · kg^-1 · min^-1; growth hormone, 10 ng · kg^-1 · min^-1; and insulin adjusted to achieve euglycemia, then constant 56 ± 7 min before exercise. Seven control subjects exercised without an IC. In four subjects (IC-1) with hormone infusions held constant during exercise, plasma insulin rose 76% and glucagon 35%, perhaps because of altered hemodynamics. In seven subjects (IC-2), hormone infusions were decreased stepwise during exercise and returned stepwise to initial rates during early recovery. R(a) increased sixfold in control and both IC groups. Plasma norepinephrine and epinephrine likewise increased >12-fold with no differences among groups; both catecholamines correlated closely with R(a). Because mixed venous blood plasma insulin declined and glucagon did not change in control subjects, the glucagon-to-insulin ratio increased from 0.20 to 0.26 (P = 0.02). In IC subjects, plasma insulin increased and glucagon was either constant (IC-2) or increased less than insulin, resulting in nonsignificant declines in the immunoreactive glucose-to-immunoreactive insulin ratio. Although a rise in insulin would have been expected to attenuate the R(a) increment, this effect was overridden. The strong correlations of R(a) with catecholamines and the similar R(a) responses despite divergent glucagon-to-insulin responses are consistent with the primacy of catecholamines in regulation of R(a) in intense exercise.