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An insulin-releasing property of imidazoline derivatives is not limited to compounds that block α-adrenoceptors

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Summary

As we have demonstrated previously phentolamine stimulates the release of additional insulin from isolated mouse islets and raises plasma insulin levels in the whole rat. This effect was independent of the well known property of phentolamine to block α-adrenoceptors.

In experiments on isolated pancreatic islets from mice we now demonstrate that tolazoline and antazoline which are chemically closely related to phentolamine, share its ability to potentiate insulin release.

The following results were taken as evidence that this effect does not result from an a-adrenoceptor blocking action of imidazoline compounds.

More than 10 times higher concentrations of phentolamine were required to liberate additional insulin from isolated islets than were effective in counteracting the inhibitory effect of clonidine on insulin release.

The newly introduced α2-adrenoceptor antagonist BDF 8933, which is an imidazoline derivative, stimulates insulin release as well, while the irreversible α-adrenoceptor blocking agent benextramine of different structure failed to do so, even when being present in concentrations blocking the α2-adrenoceptor-mediated effects of clonidine.

Antazoline shared the ability of phentolamine to stimulate insulin release despite having no or only very little α-adrenoceptor blocking activity. When used under our conditions, it almost entirely failed to alleviate the inhibition of insulin release induced by clonidine.

We conclude that the response of the islet cells to imidazoline derivatives is not limited to those capable of blocking α-adrenoceptors. On the other hand, α-adrenoceptor blocking agents of different chemical structure fail to induce the release of additional insulin. We take this as evidence that in our experiments the islet cells respond to imidazoline derivatives and not to α-adrenoceptor blockade.

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  1. Institut für Pharmakologie und Toxikologie, Universität Göttingen, Robert-Koch-Strasse 40, D-3400, Göttingen, Federal Republic of Germany

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Schulz, A., Hasselblatt, A. An insulin-releasing property of imidazoline derivatives is not limited to compounds that block α-adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 340, 321–327 (1989). https://doi.org/10.1007/BF00168517

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