Mechanisms involved in stimulation of insulin secretion by the hypoglycaemic alpha-adrenergic antagonist, DG-5128

The selective alpha 2-antagonist DG-5128 provoked a dose-dependent stimulation of insulin release from isolated rat islets. DG-5128 was only weakly effective as an antagonist of noradrenaline-induced inhibition of insulin secretion but, surprisingly, was able to reverse the suppression of secretion and increase in 86Rb efflux from preloaded islets, mediated by diazoxide. These effects were not reproduced with more effective alpha-antagonists, suggesting that stimulation of insulin secretion by DG-5128 is independent of alpha-receptor blockade.