GROWTH-HORMONE STIMULATES SKELETAL-MUSCLE PROTEIN-SYNTHESIS AND ANTAGONIZES INSULINS ANTIPROTEOLYTIC ACTION IN HUMANS

We examined the effects of a combined, local intra-arterial infusion of growth hormone (GH) and insulin on forearm glucose and protein metabolism in seven normal adults. GH was infused into the brachial artery for 6 h with a dose that, in a previous study, stimulated muscle protein synthesis (phenylalanine R(d)) without affecting systemic GH, insulin, or insulinlike growth factor I concentrations. For the last 3 h of the GH infusion, insulin was coinfused with a dose that, in the absence of infused GH, suppressed forearm muscle proteolysis by 30-40% without affecting systemic insulin levels. Measurements of forearm glucose, amino acid balance, and [H-3]phenylalanine and [C-14]leucine kinetics were made at 3 and 6 h of the infusion. Glucose uptake by forearm tissues in response to GH and insulin did not change significantly between 3 and 6 h. By 6 h, the combined infusion of GH and insulin promoted a significantly more positive net balance of phenylalanine, leucine, isoleucine, and valine (all P < 0.05). The change in net phenylalanine balance was due to a significant increase in phenylalanine R(d) (51%, P < 0.05) with no observable change in phenylalanine R(a). For leucine, a stimulation of leucine R(d) (50%, P < 0.05) also accounted for the change in leucine net balance, with no suppression of leucine R(a). The stimulation of R(d), in the absence of an observed effect on R(a), suggests that GH blunts the action of insulin to suppress proteolysis in addition to blunting insulin's action on R(d).