The Roles of Catecholamines in Glucoregulation in Intense Exercise as Defined by the Islet Cell Clamp Technique

Abstract

Exercise at > 85% VO_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 Ra, normal subjects in the postabsorptive state exercised at 87 ± 2% VO_2max during an islet cell clamp (IC): intravenous octreotide (somatostatin analog), 30 ng s· 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 < 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 Ra in intense exercise.