TUMOR-NECROSIS-FACTOR INHIBITS THE TRANSCRIPTIONAL RATE OF GLUCOSE-6-PHOSPHATASE IN-VIVO AND IN-VITRO

Recombinant human tumor necrosis factor-alpha (TNF) injection in mice was associated with a reduced blood glucose level, already manifest 6 hours following cytokine administration, Insulin levels were not affec ted. Glycogen content was decreased in a dose-dependent and time-respo nse manner, The activity of glucose-6-phosphatase (G6Pase) was already reduced 6 hours after TNF injection and was sustained 12 hours afterw ard. Phosphoenolpyruvate carboxykinase (PEPCK) activity was not affect ed initially (6 hours after injection), but a 50% reduction was observ ed 12 hours following cytokine administration compared with levels in fasting controls. Both liver G6Pase and PEPCK mRNAs were markedly redu ced due to an inhibition of the transcriptional rate. A direct inhibit ory effect of TNF on G6Pase promoter activity was demonstrated using H uH-7 cells transiently transfected with G6Pase promoter, fused to a re porter gene. Copyright (C) 1997 by W.B. Saunders Company.