WHOLE-BODY AND SPLANCHNIC LEUCINE, PHENYLALANINE, AND GLUCOSE KINETICS DURING ENDOTOXEMIA IN HUMANS

Whole body and splanchnic leucine, phenylalanine, and glucose kinetics during endotoxemia in humans. Am. J. Physiol. 266 (Regulatory Integrative Comp. Physiol. 35): R419-R425, 1994. - To examine the whole body and splanchnic tissue substrate handling during endotoxemia, an intravenous bolus of endotoxin was given to six healthy volunteers during primed, continuous infusions of [1-C-13]leucine, [ring-H-2(5)]phenylalanine, and [6,6-H-2(2)]glucose. Whole body protein breakdown, based on whole body Leu and Phe appearance rates (R(a)), increased in response to endotoxin given at time 0 (R(aLeu) 77 +/- 2 mol.kg(-1).h(-1), t = 0 h; 88 +/- 6, t = 4 h; P < 0.05) (R(aPhe) 39 +/- 2 mol.kg(-1).h(-1), t = 0; 46 +/- 3, t = 4 h; P < 0.05). Splanchnic amino acid balance (Bal) increased (Bal(Leu) 7 +/- 4 mol.kg(-1).h(-1), t = 0; 21 +/- 5, t = 2 h; P < 0.05) (Bal(Phe) 3 +/- 2 mol.kg(-1).h(-1), t = 0; 16 +/- 4, t = 2 h; P < 0.05) and can be accounted for by increased splanchnic uptake (R(d)) of Phe and Leu (Rd(Leu) 21 +/- 3 mol.kg(-1).h(-1), t = 0; 37 +/- 7, t = 120 min; P < 0.05) (R(dPhe) 10 +/- 3 mol.kg(-1).h(-1), t = 0; 24 +/- 5, t = 120 min; P < 0.05). Splanchnic conversion of Leu to ketoisocaproate increased with endotoxin administration (0.7 +/- 0.6 mol.kg(-1).h(-1), t = 0; 8 +/- 3, t = 360 min; P < 0.05). Whole body Glu production also increased (1.9 +/- 0.1 mg.kg(-1).min(-1), t = 0; 2.3 +/- 0.1, t = 120 min; P < 0.01) with splanchnic Glu production accounting for this increase (0.8 +/- 0.4 mg.kg(-1).min(-1), t = 0; 2.0 +/- 0.3, t = 120 min; P < 0.01). These data suggest that whole body proteolysis during endotoxemia is muscle related. The splanchnic extraction of amino acids and production of Glu increase during endotoxemia. Furthermore, the splanchnic bed is a site of significant Leu uptake, and during endotoxemia, is a significant site of Leu oxidation.