TUMOR-NECROSIS-FACTOR-ALPHA STIMULATES GLUCONEOGENESIS FROM ALANINE IN-VIVO

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.