EFFECTS OF ENDOTOXIN ON LEUCINE AND GLUCOSE KINETICS IN MAN - CONTRIBUTION OF PROSTAGLANDIN E(2) ASSESSED BY A CYCLOOXYGENASE INHIBITOR

The effects of endotoxin (E) administration on whole body protein and glucose metabolism were studied in normal volunteers. Injection of 4 n g/kg Escherichia coli E iv resulted in a relative increase in leucine flux (1-C-13-leucine infusion technique) compared to controls [+0.12 /- 0.10 vs. -0.45 +/- 0.23 mu mol/kg.min after 360 min, P = 0.028, ana lysis of variance (ANOVA)], indicating increased proteolysis. Nonoxida tive leucine flux was higher after E than after saline administration (0.08 +/- 0.11 vs. -0.47 +/- 0.18 mu mol/kg.min, P = 0.007, ANOVA), su ggesting increased amino acid incorporation into proteins. E caused a transient decrease of plasma glucose concentration (by 0.5 +/- 0.1 mmo l/L after 150 min; P < 0.004 vs. saline controls) due to a relative in crease in disappearance compared to appearance of glucose (6,6 D-2-glu cose infusion technique). These alterations were associated with incre ases in plasma concentrations of ACTH, beta-lipotropin (beta-LPH), GH, cortisol, epinephrine, free fatty acid, beta-hydroxybutyrate, and dec reases of plasma insulin. Pretreatment with ibuprofen, a cyclooxygenas e inhibitor, blunted the effects of E on whole body leucine flux (P < 0.05 vs. E) and on nonoxidative leucine flux (P < 0.05 vs. E) but enha nced the E-induced decrease of plasma glucose concentration (P < 0.004 vs. E), due to a relative increase in glucose disappearance compared to appearance (P = 0.02). The increases in counterregulatory hormones (ACTH, beta-LPH, GH, cortisol, epinephrine) were also attenuated by ib uprofen. Thus, acute endotoxinemia results in a redistribution of whol e body proteins due to an increase in both protein breakdown and amino acid incorporation into proteins and in decreased plasma glucose conc entrations. The ibuprofen data suggested that these effects of E on le ucine kinetics, but not on glucose metabolism, were prostaglandin E(2) -mediated.