Short-term
growth hormone excess is associated with impaired hepatic and extrahepatic responses to
insulin in the absence of a change in
insulin binding. To determine whether similar defects occur after chronic
growth hormone excess,
insulin dose-response curves for stimulation of
glucose utilization and suppression of
glucose production and monocyte and erythrocyte
insulin binding were determined in five acromegalic patients and six healthy volunteers of comparable age, sex, and
obesity. During infusion of
insulin,
glucose infusion rates required to maintain euglycemia were significantly lower (P less than 0.02 all) in the acromegalic patients than in the control subjects. Suppression of
glucose production was impaired in the acromegalic subjects at
insulin concentrations in the physiological range but not at
insulin concentrations in the supraphysiological range. In contrast stimulation of
glucose utilization was decreased in the acromegalic subjects at both physiological and supraphysiological
insulin concentrations. Neither monocyte nor erythrocyte
insulin binding differed significantly in the acromegalic and control subjects. These data indicate that chronic
growth hormone excess is associated with a defect in both hepatic and extrahepatic
insulin action. The decrease in
glucose utilization at supraphysiological
insulin concentrations in the acromegalic subjects and the normal monocyte and erythrocyte
insulin binding suggest a postbinding alteration in
insulin action.