Hepatocytes were isolated from human liver tissue by a two-step perfusion technique. They were treated with vasopressin, angiotensin, ATP and phenylephrine, which are known to be Ca2 + -mediated glycogenolytic agents in rat liver tissue, and as a control, they were treated with the cyclic AMP-mediated hormones glucagon and isoproterenol. All agonists induce a timedependent activation of glycogen phosphorylase. Glucagon and isoproterenol induce a somewhat higher degree of phosphorylase activation compared with vasopressin, angiotensin, ATP and phenylephrine, which all increase inositol tris-phosphate levels and have no effect on the cyclic AMP levels. The total activity of glycogen phosphorylase (a + b ) , amounting to 30 to 35 mU/mg protein, is found to be much lower than that found in rat liver tissue. Because only minor differences could be found, we conclude that the regulation of glycogen phosphorylase in human liver tissue is basically the same as that found in rat liver tissue. (HEPATOLOGY 1993; 17:6 10-6 14.)
Our knowledge of the short-term hormonal control of liver glycogenolysis is derived mainly from animal studies, especially from studies with perfused rat livers and isolated rat hepatocytes. On the basis of these animal studies, the glycogenolytic hormones and agonists can be classified into two groups: (a) the cyclic AMP (cAMP)-dependent agonists (i.e., glucagon, padrenergic agonists and adenosine), with CAMP as their second messenger; and (b) calcium-dependent agents (vasopressin, angiotensin 11, a,-adrenergic agonists and P,-purinergic agonists), inducing an increased concentration of inositol tris-phosphate (IP,) and of cytosolic calcium. The cyclic nucleotide leads to the activation of phosphorylase b kinase, whereas calcium ions allosterically stimulate this enzyme. Both the activated and the stimulated enzyme forms lead to the activation of