Phentolamine, a deceptive tool to investigate sympathetic nervous control of insulin release.

We investigated the effects of phentolamine and another more selective alpha 2-adrenoceptor antagonist, rauwolscine, on insulin release in vivo (in female Wistar-rats) and in vitro (in perfused rat pancreas and in isolated perifused mouse islets). Phentolamine was found to significantly increase glucose-induced insulin release. On the other hand, rauwolscine failed to do so, when applied in a concentration that effectively antagonized the inhibitory effect of clonidine. These results demonstrate that phentolamine is capable of directly stimulating insulin release. This effect is thus not mediated by alpha-adrenoceptors. For this reason phentolamine is not an appropriate tool to study possible inhibitory effects of the sympathetic nervous system on insulin release. An enhanced insulin response as may be observed in animals and in man in the presence of phentolamine does not furnish evidence for a tonic inhibitory control of the islet cells by the sympathetic nervous system.