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Midaglizole, an imidazoline derivative, is a highly selective alpha 2-adrenoceptor antagonist structurally different from the classical alpha 2-antagonist yohimbine. We compared the effects of midaglizole and yohimbine on insulin release and cAMP levels in isolated rat pancreatic islets to clarify the mechanisms underlying the hypoglycemic action of midaglizole. Midaglizole reversed epinephrine-induced inhibition of insulin release and reduction of cAMP levels, as did yohimbine. This agent, however, enhanced both insulin release and cAMP levels stimulated by glucose in the absence of epinephrine, unlike yohimbine. Moreover, the enhancing effects of midaglizole still remained, even if the action of alpha 2-adrenoceptors in the islets was blocked by pre-treatment with islet-activating protein (IAP) or by exposure to yohimbine. Under the same conditions, these effects were completely abolished by the Ca-channel blocker verapamil. The above results demonstrate that midaglizole may stimulate insulin release by the dual actions of alpha 2-adrenoceptor blockade and direct stimulation of pancreatic cAMP production.

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Stimulation of insulin release and cAMP levels in isolated rat islets by the imidazoline .ALPHA.2-adrenoceptor antagonist midaglizole: Comparison with the action of the .ALPHA.2-adrenoceptor antagonist yohimbine.