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To investigate the mechanism(s) of insulin-induced suppression of plasma amino acid concentration and release, we studied forearm as well as whole-body leucine and phenylalanine uptake and release during a peripheral insulin infusion in postabsorptive normal subjects using isotope-dilution methods. Before insulin, leucine and phenylalanine release exceeded uptake (P < 0.01 and P < 0.07, respectively). A net output of a-ketoisocaproate (KIC) was also observed. During insulin, arterial plasma leucine, KIC and phenylalanine concentrations decreased (P < 0.05 or less vs. basal), despite ongoing net output of these substrates by the forearm, that persisted after correction for the mean transit time spent through the extracellular muscular space. By the end of insulin, whole-body leucine and phenylalanine concentrations and rate of appearance were decreased (P < 0.01 vs. basal). However, release and uptake of both amino acids by the forearm were not significantly decreased vs. the preinsulin values. These data indicate that systemic hyperinsulinemia acutely decreases plasma amino acid concentrations by acting primarily at sites other than skeletal muscle. (J. Clin. Invest. 1991. 88:27-33.) Key words: amino acid uptake * amino acid release * leucine rate of appearancephenylalanine rate of appearance * net amino acid output Introduction The mechanisms by which insulin influences amino acid as well as protein turnover in vivo have been investigated with isotope dilution techniques in the last years, both in the whole body and at organ level (1-7). While there is a general agreement on the effect ofthe hormone to decrease whole-body rate of appearance (Ra)' of essential amino acids and therefore of

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