Interrelation between gluconeogenesis and hepatic protein synthesis

Acute administration of glucagon to the rat in vivo inhibits hepatic polypeptide chain elongation by about 30%. This effect was not observed in adrenalectomized rats, despite the significant increases in the hepatic content of cyclic AMP. Fatty acid administration mimics the glucagon action on protein synthesis; however, in adrenalectomized animals they were ineffective. Whether glucagon or fatty acids were administered, there was a significant increase in the state of reduction of the NAD system in normal as well as in adrenalectomized rats. This observation rules out the change in the cellular state of reduction as the mediator of their action on protein synthesis. A correlation was observed between the ability of glucagon or fatty acids to inhibit protein synthesis and to stimulate gluconeogenesis. An increased biosynthetic activity as reflected by an increased gluconeogenic flux is accompanied by a decreased phosphorylation state of adenine nucleotides that might be responsible for the inhibitory effect on protein synthesis. In adrenalectomized animals in which neither glucagon nor fatty acids stimulate gluconeogenesis, no effects on phosphorylation state or on the rate of protein synthesis were detected.This work has been supported in part by grants from Comisión Asesora de Investigación Científica y Técnica (No. 174 and 1674) and Fondo de Investigaciones Sanitarias de la Seguridad Social (No. 85/839 and 85/1321)