Effects of selective and non-selective beta-adrenergic agents on insulin secretion in vivo.

The effects of various beta-adrenergic agents on insulin secretion were investigated in vivo in mice. The non-selective beta-stimulator isopropylnoradrenaline and the selective beta 2-stimulator terbutaline both stimulated insulin secretion markedly, with the same efficacy and in a dose-dependent manner. The peak levels of plasma insulin after these two beta-agonists were achieved at a later time point (5-6 min) than after stimulation with glucose or carbachol (1.5-2.5 min). At very high dose levels the beta 2-stimulator isopropylaminothiazoloxypropanol slightly increased plasma insulin concentrations. The non-selective beta-blocker propranolol and the beta 2-selective blocker ICI 188,551 inhibited terbutaline-induced insulin release markedly and at comparable low dose levels, whereas the selective beta 1-blocker metoprolol exerted this effect only at a high dose level. At higher dose levels these three blockers moderately depressed the insulin response to glucose suggesting a partial dependence on intact beta-adrenoceptors for the effect of glucose. The beta 2-blocker butoxamine and the beta 1-blocker pamatolol did not influence insulin secretion. In conclusion, beta-adrenoceptor stimulation enhanced insulin secretion in vivo, but the beta-adrenoceptors regulating insulin secretion do not fit well into the conventional subdivision of beta 1 and beta 2, though they apparently are mainly of the beta 2-type.