Augmentation of glucose induced insulin secretion by pertussis vaccine, phentolamine and benextramine: involvement of mechanisms additional to prevention of the inhibitory actions of catecholamines in rats

Abstract

Abstract. Pertussis vaccine, pertussis toxin, and the α-adrenoceptor blocking drug phentolamine augment glucose-induced insulin secretion. The present study was carried out to determine the relationship between this action and the ability of these agents to prevent the inhibitory actions of adrenaline. Pertussis vaccine augmented glucose-induced insulin secretion in rat islets ex vivo and prevented the inhibitory actions of adrenaline and clonidine. Incubation of islets with phentolamine or the irreversible α-adrenoceptor blocking agent benextramine also augmented glucose-induced insulin secretion. However, the α-adrenoceptor blocking drugs idazoxan, yohimbine or phenoxybenzamine, in concentrations that prevented the inhibitory effects of adrenaline and/or clonidine, did not modify glucose-induced insulin release in vitro. Benextramine (1 × 10−5 mol/l) blocked the inhibitory effect of clonidine, whilst having no significant effect on the response to adrenaline. It is concluded that stimulation of insulin secretion by certain α-adrenoceptor blocking drugs can be dissociated from their α-adrenoceptor properties. The ability of pertussis vaccine, phentolamine or benextramine to augment glucose-induced insulin release in vitro is unlikely to be due to the prevention of the inhibitory action of endogenous catecholamines.