The disposal of an intravenously administered amino acid load across the human forearm

Abstract

This study was designed to examine the role of the skeletal muscle in man in the disposal of an intravenously administered L-amino acid solution. Arterio-deep venous differences of amino acids, glucose and lactate, and blood flow across the human forearm were measured in 9 healthy normal male volunteers (age = 27 ± 2 yr, weight = 79 ± 4 kg and height = 180 ± 2 cms) after an overnight fast (12 hr). Glucose and alanine turnover rates were estimated using a continuous infusion of 3- 3H-glucose and U- 14C-alanine isotopes. All measurements were obtained during steady state conditions, basally and two hours after the start of an L-amino acid infusion (8.5% solution). During the control period there was a significant release of total alpha amino nitrogen (AAN) equal to 300 ± 97 nmole 100 g forearm muscle/min with alanine and glutamine accounting for over 80% of that amount ( 260 ± 24 nmole 100 g forearm muscle/min ). The release of the branched chain amino acids (BCAA) was only significant for valine, while the release of each of the keto acids of leucine and valine, α-ketoisocaproate and α-ketoisovalerate ( 37 ± 12 and 36 ± 7 nmole 100 ml forearm muscle/min respectively ) was significant from zero and exceeded the release of the corresponding amino acids ( 13 ± 17 and 24 ± 7 nmole 100 g forearm muscle/min for leucine and valine respectively ). The infusion of the L-amino acid solution resulted in a reversal of amino acid balance across the forearm. There was a net uptake of AAN of 1195 ± 209 nmole 100 g forearm muscle/min with the BCAA accounting for 513 ± 75 nmole 100 g forearm muscle/min or 49 ± 6% of the uptake. The net uptake of BCAA by skeletal muscle did not exceed 35% of the amount infused. The release of α-ketoisocaproate and α-ketoisovalerate showed no significant change from basal levels. The output of alanine and glutamine persisted in response to the infusion; while alanine output dropped by 40%, glutamine output increased by 50% ( 68 ± 23 and 218 ± 42 nmole 100 g forearm muscle/min respectively ), yet the combined release of alanine and glutamine did not change significantly from basal levels. Amino acid infusion resulted in a twofold increase in insulin and glucagon. Plasma glucose fell from 5.3 ± 0.05 mM basally to 5.04 ± 0.06 mM ( p < 0.05), while blood lactate increased from 0.587 ± 0.03 mM to 0.639 ± 0.025 mM ( p < 0.05); similarly there was a time dependent increase in glucose uptake by muscle ( from 0.857 ± 0.08 to 1.27 ± 0.07 μ mole 100 g forearm muscle/min , p < 0.05) and lactate release ( 0.226 ± 0.03 to 0.297 ± 0.045 μ mole 100 g forearm muscle/min, p < 0.05 ). These results indicate that a significant amount of the amino acids infused, and specifically the BCAA are extracted by human skeletal muscle, and mostly retained as such for later use. The data obtained under the conditions of the present study also indicate that tissues other than skeletal muscle are as important in the overall handling of these amino acids. However, it remains to be seen whether these findings can be extrapolated to other physiological conditions.