Metabolic interactions of amino acids and glucose in healthy humans

Glucose and non-esterified fatty acids (NEFA) compete for utilization by insulin-sensitive tissues. To test whether a similar competition exists between amino acids and glucose, we infused an amino acid solution (Freamine, 0.7 g/kg) or saline during a euglycaemic insulin (1 mU/min/kg) clamp in paired fashion in a group of young, healthy volunteers. Amino acids stimulated insulin secretion (100 ± 8 vs 60 ± 5 μU/ml, p < 0.001) and inhibited whole-body glucose disposal by 26 ± 6% (24.6 ± 2.0 vs 32.7 ± 2.2 μmol/min/kg, p < 0.01). Amino acid infusion did not interfere with insulin-induced suppression of endogenous glucose production. Basal protein oxidation (estimated from urinary nitrogen excretion, 7.0 ± 0.9 μmol/min/kg) fell to 3.2 ± 1.6 μmol/min/kg (p < 0.05) during saline infusion, and increased to 13.3 ± 0.7 μmol/min/kg (p < 0.05) with amino acid administration. Correspondingly, net carbohydrate oxidation (by indirect calorimetry) rose from 6.1 ± 1.7 to 19.5 ± 1.7 μmol/min/kg (p < 0.005) under control conditions, but only from 9.1 ± 1.6 to 15.5 ± 1.2 μmol/min/kg (p < 0.05) with amino acids; thus, insulin-induced glucose oxidation was significantly inhibited by amino acid (by 7 μmol/min/kg on the average, p < 0.05). In contrast, the ability of insulin to suppress nett lipid oxidation and to enhance non-oxidative glucose disposal was not altered by amino acid infusion. A strong thermogenic effect of the infused amino acid load was documented by a rise in energy production rate from 1.11 to 1.35 kcal/min during the 2nd hour of the clamp (p < 0.01); over 2 hr, some 13% of the caloric content of Freamine was expended in this way. We conclude that, under the experimental circumstances of the present study (high amino acid and insulin concentrations) a glucose-amino acid cycle can be demonstrated, the nature and mechanisms of which appear to be essentially analogous to those of the glucose-NEFA cycle.