EFFECT OF SYSTEMIC HYPERINSULINEMIA ON AMINO-ACID FLUX ACROSS HUMAN LEGS IN POSTABSORPTIVE STATE

The effect of physiological hyperinsulinemia (approximately 110 mU/1) on leg tissue protein balance was investigated in eight weight-stable healthy individuals. A primed constant infusion of L-[U-C-14] tyrosine was used to measure the disposal and release of tyrosine across the leg before and during 2 h of euglycemic clamp studies. The leg exchange of 3-methyl-L-histidine (3-MH) and all amino acids in blood were measured before and during insulinization, including the muscle tissue content of amino acids. Hyperinsulinemia decreased whole body tyrosine flux from 52 +/- 2 to 35 +/- 1-mu-mol/min (P < 0.0001), whereas neither disposal (53 +/- 9 vs. 45 +/- 9 nmol.min-1.100 g-1) nor release of tyrosine across the leg (76 +/- 11 vs. 66 +/- 10 nmol.min-1.100 g-1) was significantly influenced. The arterial concentration and the leg exchange of 3-MH were not significantly affected by 2 h of hyperinsulinemia, but the sum of all amino acids declined significantly. The net leg balance of tyrosine was not affected at all by hyperinsulinemia, whereas the balance of the branched-chain amino acids and methionine were switched from efflux toward influx. Phenylalanine efflux from the leg only showed a trend to a significant effect by insulin. The muscle tissue concentration of six individual amino acids decreased significantly during hyperinsulinemia, particularly the branched-chain amino acids. The leg exchange of glucose, free fatty acids, and glycerol immediately changed significantly, as expected in response to insulinization. Whole body glucose uptake was 7.0 +/- 0.9 mg.min-1.kg-1 at approximately 110 mU/l plasma insulin. The results demonstrate that physiological systemic hyperinsulinemia did not significantly affect either the overall protein synthesis or breakdown across leg tissues as recently reported for forearm muscles during local hyperinsulinemia.