Insulin sensitivity of protein and glucose metabolism in human forearm skeletal muscle

Physiologic increases of insulin promote net amino acid uptake and protein anabolism in forearm skeletal muscle by restraining protein degradation. The sensitivity of this process to insulin is not known. Using the forearm perfusion method, we infused insulin locally in the brachial artery at rates of 0.00 (saline control), 0.01, 0.02, 0.035, or 0.05 mU/min per kg for 150 min to increase local forearm plasma insulin concentration by 0, ∼20, ∼35, ∼60, and ∼120 μU/ml (n = 35). L-[ring-2,6-³H]phenylalanine and L-[1-¹⁴C]leucine were infused systemically, and the net forearm balance, rate of appearance (R_a) and rate of disposal (R_d) of phenylalanine and leucine, and forearm glucose balance were measured basally and in response to insulin infusion. Compared to saline, increasing rates of insulin infusion progressively increased net forearm glucose uptake from 0.9 μmol/min per 100 ml (saline) to 1.0, 1.8, 2.4, and 4.7 μmol/min per 100 ml forearm, respectively. Net forearm balance for phenylalanine and leucine was significantly less negative than basal (P < 0.01 for each) in response to the lowest dose insulin infusion, 0.01 mU/min per kg, and all higher rates of insulin infusion. Phenylalanine and leucine R_a declined by ∼38 and 40% with the lowest dose insulin infusion. Higher doses of insulin produced no greater effect (decline in R_a varied between 26 and 42% for phenylalanine and 30-50% for leucine). In contrast, R_d for phenylalanine and leucine did not change with insulin. We conclude that even modest increases of plasma insulin can markedly suppress proteolysis, measured by phenylalanine R_a, in human forearm skeletal muscle. Further increments of insulin within the physiologic range augment glucose uptake but have little additional effect on phenylalanine R_a or balance. These results suggest that proteolysis in human skeletal muscle is more sensitive than glucose uptake to physiologic increments in insulin.