ON THE ACTION OF TOLBUTAMIDE IN NORMAL MAN

Abstract

ABSTRACT The plasma insulin response to intravenously administered tolbutamide was measured in healthy subjects under experimentally induced variations in the blood glucose concentration. Decreasing blood glucose concentration down to 51 and 25% of the basal level by the iv administration of 0.05 and 0.10 IU of insulin/kg body weight, respectively, resulted in significant inhibition of the insulin response to tolbutamide. The degree of inhibition was correlated to the extent of the hypoglycaemia. This inhibition seems to be only partially mediated by catecholamines, since blocking the α-adrenergic receptors with phentolamine could not restore the action of tolbutamide. Furthermore, whereas the prevention of the hypoglycaemia that normally follows tolbutamide administration resulted in an enhancement of the insulin response to the drug, phentolamine had no such effect. These results indicate that the decrease in blood glucose concentration as such, rather than activation of the adrenergic mechanisms, is responsible for the inhibition of tolbutamide-induced insulin release. Hence, the blood glucose level at the time of tolbutamide administration seems to determine the insulin response to the drug. The administration of the β-adrenergic blocking agent propranolol, in doses known to suppress glucose-induced insulin release in man, had no effect on the insulin response to tolbutamide. Our studies thus do not confirm the reports of other investigators that sulphonylureas may act on the islet cell as β-adrenergic agonists.