STARVATION AND ENDOTOXIN ACT INDEPENDENTLY AND SYNERGISTICALLY TO COORDINATE HEPATIC GLUTAMINE TRANSPORT

Objective: Because hepatic glutamine transport is markedly enhanced du ring critical illness, we tested the hypothesis that nutrient starvati on and endotoxemia act coordinately to augment transport activity, Des ign: Fed or starved (48 hours) rats received Escherichia coli endotoxi n (LPS, 10 mg/kg of body weight, intraperitoneally) or saline before h epatocyte isolation for measurement of glutamine transport, Materials and Methods: Hepatocytes were isolated from fed or fasted rats 4 hours after LPS treatment, [H-3]glutamine uptake was measured and normalize d to cellular protein, Data (mean +/- standard deviation, three separa te determinations) were analyzed by Student's t test and analysis of v ariance. Main Results: Starvation induced a 1.6-fold increase in gluta mine transport, while LPS treatment of fed rats increased transport ac tivity 2.6-fold, Treatment of fasted animals with LPS induced a sixfol d increase in glutamine transport, Kinetically, this effect in endotox emic starved rats was mediated by both an increase in System N V-max a nd the induction of a high affinity System A amino acid carrier which transports glutamine, Conclusions: Starvation and endotoxemia regulate hepatocyte glutamine transport independently and synergistically, Thi s hepatic response provides glutamine and other amino acids to support key metabolic pathways in the liver during critical illness.