Effects of insulin on phenylephrine-induced activation of phosphorylase and phosphatidylinositol turnover in isolated hepatocytes.

Treatment of isolated hepatocytes with the alpha-agonist phenylephrine led to a rapid increase in the activity of phosphorylase a and an increase in the rate of 32P incorporation into phosphatidylinositol. After pretreatment of the cells with insulin, this activation of phosphorylase was reduced by about 50% but there was no alteration in either the basal or phenylephrine-stimulated rate of phosphatidylinositol turnover. This difference in the sensitivity of these two processes to insulin was observed at all times and concentrations of phenylephrine examined. Direct measurement of phosphatidylinositol breakdown and phosphatidic acid formation confirmed that the activation of the phosphatidylinositol cycle by phenylephrine was not blocked by insulin. These data suggest that insulin antagonism of alpha-adrenergic effects on glycogenolysis in liver is mediated at a step distal to hormone binding to the alpha 1-receptor and activation of inositol lipid breakdown but prior to intracellular Ca2+ mobilization.