Hepatic glutamine transporter activation in burn injury: role of amino acids and phosphatidylinositol-3-kinase

Burn injury elicits a marked, sustained hypermetabolic state in patients ch aracterized by accelerated hepatic amino acid metabolism and negative nitro gen balance. The transport of glutamine, a hey substrate in gluconeogenesis and ureagenesis, was examined in hepatocytes isolated from the livers of r ats after a 20% total burn surface area full-thickness scald injury. A late nt and profound two- to threefold increase in glutamine transporter system N activity was first observed after 48 h in hepatocytes from injured rats c ompared with controls, persisted for 9 days, and waned toward control value s after 18 Bays, corresponding with convalescence. Further studies showed t hat the profound increase was fully attributable to rapid posttranslational transporter activation by amino acid-induced cell swelling and that this f orm of regulation may be elicited in part by glucagon. The phosphatidylinos itol-3-kinase (PI3K) inhibitors wortmannin and LY-294002 each significantly attenuated transporter stimulation by amino acids. The data suggest that P I3K-dependent system N activation by amino acids may play an important role in fueling accelerated hepatic nitrogen metabolism after burn injury.