GLUCAGON ADMINISTRATION IN-VIVO STIMULATES HEPATIC RNA AND PROTEIN BREAKDOWN IN FED AND FASTED RATS

Liver RNA and protein breakdown rates were measured simultaneously in fed and in 24 h-fasted rats during a short-term cyclic perfusion, 1 h after an intraperitoneal injection of glucagon or of saline. RNA was l abelled in vivo by an intraperitoneal injection of [6-C-14]orotic acid , 60 h before the start of the perfusion. The accumulation of radioact ive cytidine and valine in the perfusion medium for 15 min was used to determine RNA breakdown and proteolysis respectively. The portal gluc agon/ insulin ratio was significantly higher in the fasted glucagon-tr eated rats than in their fed counterparts. Although glucagon administr ation significantly increased RNA and protein degradation rates in the fasted and in the fed groups, the effect was greater after 24 h of st arvation. The relationship between these biochemical changes and the a lterations of the hepatocyte lysosomal system was investigated by dete rmining the fractional cytoplasmic volume of lysosomal structures (aut ophagic vacuoles and dense bodies) by morphometry in the fasted glucag on-treated rats and in their controls. Hyperlucagonaemia significantly enhanced the relative volume of autophagic vacuoles without affecting that of dense bodies. The results showed that hyperglucagonaemia indu ced in vivo stimulated both liver RNA and protein breakdown and that t his effect was modulated by the nutritional status of the rats.