Leucine and phenylalanine kinetics in compensated liver cirrhosis: effects of insulin.

BACKGROUND: The pathogenesis of the altered ratio of branched-chain amino acid to aromatic amino acid concentration in liver cirrhosis is poorly known. We explored the possible link between altered amino acid concentrations and kinetics in cirrhosis.
METHODS: Post-absorptive leucine and phenylalanine rates of appearance (Ra) and their response to insulin were studied in patients with compensated, nondiabetic cirrhosis and in controls.
RESULTS: In the cirrhotics, concentration of postabsorptive phenylalanine was greater and that of alpha-ketoisocaproate lower than in controls, whereas concentration of leucine was comparable. Leucine Ra was lower, phenylalanine Ra was greater, and the ratio of leucine Ra to phenylalanine Ra was markedly decreased (P < 0.001) in patients vs. controls (2.40 +/- 0.23 vs. 3.67 +/- 0.19, respectively). During an euglycemic-hyperinsulinemic clamp, glucose disposal was reduced and leucine Ra was suppressed more profoundly in cirrhotics than in controls, whereas suppression of phenylalanine Ra was comparable.
CONCLUSIONS: In compensated liver cirrhosis, postabsorptive phenylalanine Ra is increased with respect to leucine Ra, suggesting the existence either of altered amino acid pools and/or transport or of abnormally sequenced proteins and/or peptides. Insulin resistance is restricted to glucose, but not to amino acid metabolism.