The properties of imidazoline derivatives to stimulate insulin release by hamster pancreatic islets are probably due to alpha 2-adrenoceptor blockade but not to interaction with non-adrenergic idazoxan binding sites.

The present study attempts to define the roles of alpha 2-adrenoceptors and of non-adrenergic idazoxan binding sites on insulin release using various alpha 2-adrenoceptor blocking agents belonging to the imidazoline family or not. Experiments were performed either on freshly isolated or on 24 h-cultured pancreatic islets from adult male hamsters. Neither the densities of alpha 2-adrenoceptors and non adrenergic idazoxan binding sites nor the response to the alpha 2-agonist, clonidine, were changed after the survival period. The effect of various alpha 2-antagonists: idazoxan, RX821002, phentolamine and yohimbine on the rate of insulin release was investigated. On freshly isolated islets, the imidazoline compounds stimulated insulin release while yohimbine did not. Nevertheless, this stimulation was no more observed with any of these compounds when tested on islets maintained in survival for 24 h. The measurement of catecholamines indicated that the level of noradrenaline was high in freshly isolated islets while it was undetectable after 24 h-culture. Taken together these results suggest that alpha 2-antagonists stimulate insulin release by relieving the beta-cell from the inhibitory effect of prebound endogenous catecholamines.