Inhibition of dibutyryl cyclic AMP-induced insulin release by alpha-2 adrenergic stimulation

Effects of alpha adrenergic agonists and antagonists on dibutyryl cAMP (Bt2cAMP)-induced insulin release were investigated with isolated rat pancreatic islets. Bt2cAMP (4 mM) produced 2-fold stimulation of insulin release in all the concentrations of glucose examined (3.3-16.7 mM). Clonidine but not phenylephrine inhibited the Bt2cAMP-stimulated insulin release in a concentration-dependent manner with approximate EC50 of nanomolar range. Yohimbine but not prazosin antagonized the inhibitory effect of clonidine on the Bt2-cAMP-induced insulin release. These results suggest that alpha-2 adrenergic mechanisms are involved in a step distal to cAMP generation.