Effects of branched-chain-enriched amino acids and insulin on forearm leucine kinetics

Although amino acid mixtures enriched in branched-chain amino acids (BCAA) and deficient in aromatic amino acids (AAA) are often used together with insulin and glucose in clinical nutrition, their physiological effects on muscle protein anabolism are not known. To this aim, we studied forearm leucine kinetics in post-absorptive volunteers, before and after the systemic infusion of BCAA-enriched, AAA-deficient amino acids along with insulin and the euglycaemic clamp. The results were compared with the effects of insulin infusion alone. A compartmental leucine forearm model was employed at steady state. Hyperaminoacidaemia with hyperinsulinaemia (to approximately 80-100 micro-units/ml) increased the leucine plasma concentration (+70%; P<0.001), inflow into the forearm cell (+150%; P<0.01), disposal into protein synthesis (+100%; P<0.01), net intracellular retention (P<0.01), net forearm balance (by approximately 6-fold; P<0.01) and net deamination to alpha-ketoisocaproate (4-methyl-2-oxopentanoate) (+9%; P<0.05). Leucine release from forearm proteolysis and outflow from the forearm cell were unchanged. In contrast, hyperinsulinaemia alone decreased plasma leucine concentrations (-35%; P<0.001) and leucine inflow (-20%; P<0.05) and outflow (-30%; P<0.01) into and out of forearm cell(s), it increased net intracellular leucine retention (P<0.03), and it did not change leucine release from forearm proteolysis (-20%; P=0.138), net leucine deamination to alpha-ketoisocaproate, leucine disposal into protein synthesis or net forearm protein balance. By considering all data together, leucine disposal into protein synthesis was directly correlated with leucine inflow into the cell (r=0.71; P<0.0001). These data indicate that the infusion of BCAA-enriched, AAA-deficient amino acids along with insulin is capable of stimulating forearm (i.e. muscle) protein anabolism in normal volunteers by enhancing intracellular leucine transport and protein synthesis. These effects are probably due to hyperaminoacidaemia and/or its interaction with hyperinsulinaemia, since they were not observed under conditions of hyperinsulinaemia alone.