Muscle sympathetic nerve activity in patients with acromegaly

Muscle sympathetic nerve activity was measured in nine acromegalic patients (age, 35 ± 4 yr; body mass index, 28 ± 2 kg/m²) and eight healthy subjects (age, 32 ± 3 yr; body mass index, 25 ± 2 kg/m²) by combining the forearm arterial-venous difference technique with the tracer method [infusion oftritiated norepinephrine (NE)]. Muscle NE release was quantified both at rest and during physiological hyperinsulinemia while maintaining euglycemia (~90 mg/dL) by means of the euglycemic clamp. Arterial plasma NE was similar in the two groups at rest (197 ± 28 and 200 ± 27 pg/mL^-1) and slightly increased during insulin infusion. Forearm NE release was 2.33 ± 0.55 ng-liter^-1·min^-1 in healthy subjects and 2.67 ± 0.61 ng·liter^-1·min^-1 in acromegalic subjects in the basal state and increased to a similar extent during insulin infusion in both groups (3.13 ± 0.71 and 3.32 ± 0.75 ng·L^-1. min^-1, P < 0.05 vs. basal), indicating a normal stimulatory effect of insulin on muscle sympathetic activity. In contrast, insulin-stimulated forearm glucose uptake was markedly lower in acromegalic patients (2.3 ± 0.4 mg·L^-1·min^-1) than in control subjects (7.9 ± 1.3 mg·L^-1·min^-1, P < 0.001), indicating the presence of severe insulin resistance involving glucose metabolism. Our data demonstrate that patients with long-term acromegaly have normal sympathetic activity in the skeletal muscle in the basal, postabsorptive state and normal increments in NE spillover in response to the sympatho-excitatory effect of insulin. Thus, the presence of severe insulin resistance in acromegaly is not accounted for by adrenergic mechanisms.