Inhibition by catecholamines of the induction of rat liver glucokinase.

Epinephrine, norepinephrine, and isoproterenol prevent the induction of rat liver glucokinase (EC 2.7.1.2) produced by the administration of glucose to animals with low levels of the enzyme. The low levels of glucokinase were obtained by feeding the animals a carbohydrate-free diet for 6 days. When epinepbrine was given 4 hours after the administration of carbohydrate there was only a slight inhibition of the rate of enzyme increase, whereas when given simultaneously with the carbohydrate there was a complete blockade of the induction. The N6, 02’-dibutyryl analogue of cyclic adenosine 3’,5’-monophosphate also inhibited glucokinase induction. Insulin counteracted about 50% of the epinephrine effect, but not the hihibition elicited by dibutyryl cyclic AMP. The data suggest that the epinephrine action on glucokmase induction may result both from a direct effect on the liver cell, possibly mediated by cyclic AMP, and a blockade of insulin secretion at the pancreas.