ON THE ACTION OF TOLBUTAMIDE IN NORMAL MAN

Abstract

ABSTRACT Previous studies in normal man suggest that tolbutamide exerts its insulinogenic effect by modulating glucose-induced insulin release. This is probably achieved by increasing the sensitivity of the β-cells to the action of glucose in eliciting an insulinogenic signal, rather than by influencing the glucose metabolism of the islets. The present paper reports on studies on the relation of tolbutamide to the cyclic AMP system of the islets. Aminophylline, which decreases the breakdown of cyclic AMP, was without effect on tolbutamide-induced insulin release. This indicates that tolbutamide probably does not act by stimulating adenyl cyclase. In contrast, the insulin response to glucagon, an agent known to stimulate adenyl cyclase, was markedly potentiated by tolbutamide. Tolbutamide. in this respect, also showed synergism with arginine, which probably acts by enhancing the formation of cyclic AMP. It is therefore concluded that tolbutamide may influence insulin release by acting as a phosphodiesterase inhibitor or as a potentiator of the action of cyclic AMP on the release mechanisms. The possible relationship of the tolbutamide action with the postulated insulinogenic signal of glucose in the β-cell is discussed.