Comparative effect of glucagon and isoproterenol on hepatic glycogenolysis and glycolysis in isolated perfused liver

The effect of glucagon and isoproterenol (beta-adrenergic agonist) on hepatic glycogenolysis and glycolysis in isolated perfused liver was compared. The levels of isoproterenol and glucagon which promoted the maximal activation of glycogenolysis were 20 muM and 1nM respectively. However, glucagon (1 nM) not only increased glycogenolysis but also inhibited glycolysis. Because adenosine-3'-5'-cyclic monophosphate (cAMP) is a common second messenger to glucagon and isoproterenol, the level of cAMP that simulates the effect of these substances were investigated. The concentration of cAMP that inhibited glycolysis was five times higher (15 muM) than that which stimulated glycogenolysis (3 muM). Similar inhibition of glycolysis was obtained with cAMP agonists resistant to phosphodiesterases, i.e., 8-Br-cAMP and N6-monobutyryl-cAMP (6-MB-cAMP) at the concentration of 3 muM. Thus, apparently glucagon could produce higher cellular levels of cAMP than that obtained with the activation of beta-adrenergic receptors. The higher amount of cAMP could be enough to overcome the action of phosphodiesterases and penetrate in the cytosol creating a favourable gradient to inhibit the enzymes of glycolysis