EFFECT OF CORTISOL ON ENERGY-EXPENDITURE AND AMINO-ACID-METABOLISM INHUMANS

Hydrocortisone was infused overnight into nine normal healthy adults o n three occasions at 0, 80, and 200 mu g.kg(-1).h(-1), producing plasm a cortisol concentrations of 10.6 +/- 1.2, 34.0 +/- 2.0, and 64.9 +/- 4.3 mu g/dl, respectively. L-[1-C-13]leucine, L-[phenyl-H-2(5)]phenyla lanine, and L-[2-N-15]glutamine were infused during the last 7 h of hy percortisolemia to measure amino acid kinetics. During the last 3.5 h, somatostatin, glucagon, and insulin were infused to reduce the cortis ol-induced elevation in plasma insulin to basal. Hypercortisolemia inc reased plasma glucose, free fatty acid (FFA), and insulin concentratio ns. Institution of the somatostatin clamp returned insulin to basal bu t increased glucose and FFA. Acute hypercortisolemia increased protein breakdown 5-20%, as measured by increases in leucine and phenylalanin e appearance rates. Normalizing insulin during hypercortisolemia did n ot alter phenylalanine flux but en hanced leucine appearance rate, the latter result indicating that insulin was affecting leucine metabolis m during hypercortisolemia. The fraction of the leucine flux that was oxidized was not significantly increased with hypercortisolemia, but d isposal by the nonoxidative route of leucine uptake for protein synthe sis was increased. Hypercortisolemia increased cycling of amino acids by increasing protein breakdown and synthesis, but the increase in thi s process could have increased resting energy expenditure (REE) only 1 -2%. Hypercortisolemia increased glutamine flux in a dose-dependent fa shion through an increase in de novo synthesis, which presumably refle cts increased release from skeletal muscle. Hypercortisolemia increase d REE 9-15% at the 80 and 200 mu g.kg(-1).h(-1) infusion rates. Respir atory quotient did not rise with cortisol infusion but tended to decre ase, suggesting that the increase in REE was fueled by increased oxida tion of fat. These data demonstrate that hypercortisolemia increases m etabolic rate and may be in part responsible for the hypermetabolic st ate in injury.