Tumor necrosis factor alpha stimulates gluconeogenesis from alanine in vivo

✍ Scribed by David Blumberg; Steven Hochwald; Michael Burt; David Donner; Dr. Murray F. Brennan

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 561 KB
• Volume: 59
• Category: Article
• ISSN: 0022-4790
• DOI: 10.1002/jso.2930590404

✦ Synopsis

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 a (TNFa) may mediate this cachexia, we examined the effect of this cytokine on gluconeogenesis. Twenty-eight male Fischer rats were injected intraperitoneally with TNFa (250 Fgikg) 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. TNFa 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 TNFa injection ( P < 0.05). In vivo TNFa causes an increase in hepatic gluconeogenesis associated with increased plasma glucagon.