Growth Hormone Stimulates Skeletal Muscle Protein Synthesis and Antagonizes Insulin's 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 [³H]phenylalanine and [¹⁴C]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 Ra. The stimulation of R_d, in the absence of an observed effect on Ra, suggests that GH blunts the action of insulin to suppress proteolysis in addition to blunting insulin's action on R_d.