Tumor necrosis factor alpha stimulates gluconeogenesis from alanine in vivo.
An increase in gluconeogenesis contributes to the cachexia seen in severe injury, sepsis, and malignancy by converting amino acids from skeletal muscle to glucose. Since tumor necrosis factor alpha (TNF alpha) may mediate this cachexia, we examined the effect of this cytokine on gluconeogenesis. Twenty-eight male Fischer rats were injected intraperitoneally with TNF alpha (250 micrograms/kg) or saline, and after 4 hours, isolated hepatocytes were obtained by in situ collagenase liver perfusion. Hepatocytes were incubated with alanine (10 mM), and rates of gluconeogenesis were determined. Plasma lactate, glucose, insulin, glucagon, cortisol, and amino acids were measured. TNF alpha administration resulted in a 50% increase in gluconeogenesis from alanine (P < 0.05) and a three-fold increase in plasma glucagon (P = 0.01). Total and glucogenic plasma amino acids decreased with TNF alpha injection (P < 0.05). In vivo TNF alpha causes an increase in hepatic gluconeogenesis associated with increased plasma glucagon.
Blumberg
D
D
Surgical Metabolism Laboratory, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Hochwald
S
S
Burt
M
M
Donner
D
D
Brennan
M F
MF
D000409:Alanine / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005934:Glucagon / Q000097:blood; D005943:Gluconeogenesis / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014022:Tissue Survival; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D005934:Glucagon; D000409:Alanine