Effects of Glucagon on General Protein Degradation and Synthesis in Perfused Rat Liver

Abstract The direct influence of glucagon on rates of valine incorporation into and release from protein was assessed in the perfused rat liver. Glucagon alone significantly increased net valine release, an effect which was ascribed largely to the stimulation of proteolysis. The magnitude of this increase in absolute terms remained virtually unchanged in the presence of an amino acid mixture that suppressed proteolysis. The increase was also obtained in the presence of sufficient cycloheximide to inhibit valine incorporation by 93 %. In addition, free intracellular valine was elevated relative to external values over an 8-fold range of perfusate valine concentration. Rates of valine incorporation into liver protein were reduced by glucagon alone to a small but significant degree. Of interest, however, was the finding that the inhibition was potentiated by additions of amino acids. In the presence of a complete amino acid mixture, simulating the composition of plasma amino acids at 10 times their normal concentrations, glucagon strongly depressed valine incorporation, and the rate was comparable to the value obtained previously when the amino acid supply was severely limited. These findings suggest that the turnover of liver proteins is regulated by glucagon at sites of both protein degradation and synthesis.