IntroductionPhysiologic 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 ,U/ml (n = 35). L-Iring-2,6-3Hjphenylalanine and L-11-14Cjleucine were infused systemically, and the net forearm balance, rate of appearance (R.) and rate of disposal (Rd) 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 Mmol/min per 100 ml (saline) to 1.0, 1.8, 2.4, and 4.7 ,umol/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. The effects ofhyperinsulinemia on skeletal muscle, the largest pool of protein in the body, has been of particular interest. Pozefsky et al. (9), using the forearm perfusion technique, observed that local hyperinsulinemia diminished net forearm amino acid release and stimulated glucose uptake. With direct infusion of insulin into the brachial artery, the effects of hyperinsulinemia on forearm skeletal muscle metabolism can be examined directly (9-13) without the confounding influence of altered substrate concentrations that accompany systemic insulin administration (14,15