1. Tumor necrosis factor inhibits the transcriptional rate of glucose-6-phosphatase in vivo and in vitro
- Author
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Eitan Shiloni, Varda Barash, Tamar Peretz, Nachum Begleibter, Tova Chajek-Shaul, Olga Drize, and Shula Metzger
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Necrosis ,Transcription, Genetic ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Mice ,chemistry.chemical_compound ,Endocrinology ,In vivo ,Internal medicine ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Insulin ,Promoter Regions, Genetic ,biology ,Glycogen ,Tumor Necrosis Factor-alpha ,Recombinant Proteins ,Mice, Inbred C57BL ,Cytokine ,Liver ,chemistry ,Glucose-6-Phosphatase ,biology.protein ,Phosphoenolpyruvate Carboxykinase (GTP) ,Tumor necrosis factor alpha ,medicine.symptom ,Phosphoenolpyruvate carboxykinase ,Glucose 6-phosphatase - Abstract
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 affected. Glycogen content was decreased in a dose-dependent and time-response manner. The activity of glucose-6-phosphatase (G6Pase) was already reduced 6 hours after TNF injection and was sustained 12 hours afterward. Phosphoenolpyruvate carboxykinase (PEPCK) activity was not affected initially (6 hours after injection), but a 50% reduction was observed 12 hours following cytokine administration compared with levels in fasting controls. Both liver G6Pase and PEPCK mRNAs were markedly reduced due to an inhibition of the transcriptional rate. A direct inhibitory effect of TNF on G6Pase promoter activity was demonstrated using HuH-7 cells transiently transfected with G6Pase promoter, fused to a reporter gene.
- Published
- 1997