Time sequence of changes in the responsiveness of glycogen breakdown to adrenergic agonists in perfused liver of rats with insulin-induced hypoglycemia

The time-course changes of the responsiveness of glycogen breakdown to alph a- and beta-adrenergic agonists during insulin-induced hypoglycemia (IIH) w ere investigated. Blood glucose levels were decreased prior to the alterati on in the hepatic responsiveness to adrenergic agonists. The activation of hepatic glucose production and glycogenolysis by phenylephrine (2 mu M) and isoproterenol (20 mu M) was decreased in IM. The changes in the responsive ness of glycogen catabolism were first observed for isoproterenol and later for phenylephrine. Hepatic beta-adrenergic receptors showed a higher degre e of adrenergic desensitization than did alpha-receptors. Liver glycogen sy nthase activity, glycogen content and the catabolic effect of dibutyryl cyc lic AMP (the beta-receptor second messenger) were not affected by IIH.