Effect of leucine on amino acid and glucose metabolism in humans

Leucine has been reported to be an important regulator of protein metabolism. We investigated the effect of intravenous infusion of l-leucine versus saline on amino acid metabolism in eight healthy human subjects. Plasma concentrations of amino acids were measured and protein turnover was estimated using l-(1-¹³C)lysine and l-(3,3,3-²H₃)leucine as tracers. Glucose kinetics were measured using d-(6,6-²H₂)glucose as a tracer. Leucine infusion increased the plasma leucine concentration from 103 ± 8 to 377 ± 35 μmol/L (P < .01). Plasma concentrations of essential amino acids, including threonine, methionine, isoleucine, valine, tyrosine, and phenylalanine were significantly decreased by leucine infusion. Leucine infusion did not change lysine flux significantly (108 ± 4 during saline v 101 ± 4 μmol/kg/h^-1 during leucine infusion), but decreased lysine oxidation (13.2 ± 0.9 v 10.7 ± 1 μmol/kg/h, P < .05) and endogenous leucine flux (from 128 ± 4 to 113 ± 7 μmol/kg/h, P < .05) when plasma (²H₃) ketoisocaproate (KIC) was used for calculation. During leucine infusion, the (²H₃) KIC to (²H₃) leucine plasma enrichment ratio increased from 0.76 ± 0.02 to 0.88 ± 0.01 (P < .001), while estimation of leucine flux using plasma (²H₃) leucine showed no change in endogenous leucine flux. Leucine infusion decreased hepatic glucose production and metabolic clearance of glucose, but did not change plasma concentrations of glucose, insulin, C-peptide, glucagon, epinephrine, norepinephrine, or free fatty acids. We conclude that leucine spares glucose and lysine catabolism and decreases plasma concentrations of essential amino acids. This study also demonstrated that the ratio of plasma KIC enrichment to leucine enrichment does not remain constant in all study conditions.