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 characterized by accelerated hepatic amino acid metabolism and negative nitrogen balance. The transport of glutamine, a key substrate in gluconeogenesis and ureagenesis, was examined in hepatocytes isolated from the livers of rats after a 20% total burn surface area full-thickness scald injury. A latent and profound two- to threefold increase in glutamine transporter system N activity was first observed after 48 h in hepatocytes from injured rats compared with controls, persisted for 9 days, and waned toward control values after 18 days, corresponding with convalescence. Further studies showed that the profound increase was fully attributable to rapid posttranslational transporter activation by amino acid-induced cell swelling and that this form of regulation may be elicited in part by glucagon. The phosphatidylinositol-3-kinase (PI3K) inhibitors wortmannin and LY-294002 each significantly attenuated transporter stimulation by amino acids. The data suggest that PI3K-dependent system N activation by amino acids may play an important role in fueling accelerated hepatic nitrogen metabolism after burn injury.
Pawlik
T M
TM
Surgical Oncology Research Laboratories, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114-2696, USA.
Lohmann
R
R
Souba
W W
WW
Bode
B P
BP
D000596:Amino Acids / Q000502:physiology; D000818:Animals; D001692:Biological Transport; D002056:Burns / Q000097:blood / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D005934:Glucagon / Q000097:blood; D005973:Glutamine / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
D000596:Amino Acids; D002352:Carrier Proteins; D007328:Insulin; D005973:Glutamine; D005934:Glucagon; D019869:Phosphatidylinositol 3-Kinases