Gluconeogenesis in the liver of arthritic rats

The gluconeogenic response in the liver from rats with chronic arthritis to various substrates and the effects of glucagon were investigated. The experimental technique used was the isolated liver perfusion. Hepatic gluconeogenesis in arthritic rats was generally lower than in normal rats. The difference between normal and arthritic rats depended on the gluconeogenic substrate. In the absence of glucagon the following sequence of decreasing differences was found: alanine (−71·8 per cent)∽glutamine (−71·7 per cent)>pyruvate (−60 per cent)>lactate+pyruvate (−44·9 per cent)>xylitol (n.s.=non‐significant)∽glycerol (n.s.). For most substrates glucagon increased hepatic gluconeogenesis in both normal and arthritic rats. The difference between normal and arthritic rats, however, tended to diminish, as revealed by the data of the following sequence: alanine (−48·9 per cent)∽pyruvate (−47·6 per cent)>glutamine (−33·8 per cent)>glycerol (n.s.)∽lactate+pyruvate (n.s.)∽xylitol (n.s.). The causes for the reduced hepatic gluconeogenesis in arthritic rats are probably related to: (a) lower activities of key enzymes catalyzing most probably steps preceding phosphoenolpyruvate (e.g. phosphoenolpyruvate carboxykinase, pyruvate carboxylase, etc.); (b) a reduced availability of reducing equivalents in the cytosol; (c) specific differences in the situations induced by hormones or by the individual substrates. Since glycaemia is almost normal in chronically arthritic rats, it seems that lower gluconeogenesis is actually adapted to the specific needs of these animals. Copyright © 1999 John Wiley & Sons, Ltd.