D. Blumberg et al., TUMOR-NECROSIS-FACTOR-ALPHA STIMULATES GLUCONEOGENESIS FROM ALANINE IN-VIVO, Journal of surgical oncology, 59(4), 1995, pp. 220-225
An increase in gluconeogenesis contributes to the cachexia seen in sev
ere injury, sepsis, and malignancy by converting amino acids from skel
etal 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 intraper
itoneally with TNF alpha (250 mu g/kg) or saline, and after 4 hours, i
solated hepatocytes were obtained by in situ collagenase liver perfusi
on. Hepatocytes were incubated with alanine (10 mM), and rates of gluc
oneogenesis were determined. Plasma lactate, glucose, insulin, glucago
n, cortisol, and amino acids were measured. TNF alpha administration r
esulted in a 50% increase in gluconeogenesis from alanine (P < 0.05) a
nd a three-fold increase in plasma glucagon (P = 0.01). Total and gluc
ogenic plasma amino acids decreased with TNF alpha injection (P < 0.05
). In vivo TNF alpha causes an increase in hepatic gluconeogenesis ass
ociated with increased plasma glucagon. (C) 1995 Wiley-Liss, Inc.