Effects of endotoxin on leucine and glucose kinetics in man: contribution of prostaglandin E2 assessed by a cyclooxygenase inhibitor

Abstract

The effects of endotoxin (E) administration on whole body protein and glucose metabolism were studied in normal volunteers. Injection of 4 ng/kg Escherichia coli E iv resulted in a relative increase in leucine flux (1-13C-leucine infusion technique) compared to controls [+0.12 +/- 0.10 vs. -0.45 +/- 0.23 mumol/kg.min after 360 min, P = 0.028, analysis of variance (ANOVA)], indicating increased proteolysis. Nonoxidative leucine flux was higher after E than after saline administration (0.08 +/- 0.11 vs. -0.47 +/- 0.18 mumol/kg.min, P = 0.007, ANOVA), suggesting increased amino acid incorporation into proteins. E caused a transient decrease of plasma glucose concentration (by 0.5 +/- 0.1 mmol/L after 150 min; P < 0.004 vs. saline controls) due to a relative increase in disappearance compared to appearance of glucose (6,6 D2-glucose infusion technique). These alterations were associated with increases in plasma concentrations of ACTH, beta-lipoprotein (beta-LPH), GH, cortisol, epinephrine, free fatty acid, beta-hydroxybutyrate, and decreases of plasma insulin. Pretreatment with ibuprofen, a cyclooxygenase 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 enhanced 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 ibuprofen. Thus, acute endotoxinemia results in a redistribution of whole body proteins due to an increase in both protein breakdown and amino acid incorporation into proteins and in decreased plasma glucose concentrations. The ibuprofen data suggested that these effects of E on leucine kinetics, but not on glucose metabolism, were prostaglandin E2-mediated.