Calcium mobilization, prostaglandin E₂ and α₂-adrenoceptor modulation of glucose utilization and insulin secretion in pancreatic islets

α₂-Adrenoceptor agonists inhibit glucose-stimulated insulin release and glucose utilization in pancreatic islets. In isolated pancreatic islets of the rat, the Ca²⁺ channel agonists CGP-28392 and BAY-K-8644 increased insulin release in the presence of clonidine. Neither CGP-28392 nor BAY-K-8644 antagonized the effect of clonidine on glucose utilization. The Ca²⁺ ionophore, ionomycin, also did not affect glucose utilization in the presence or absence of clonidine. Glucagon partly reversed the effects of clonidine on insulin release, and it potentiated glucose-stimulated insulin release in the absence of clonidine. Glucagon reversed the effects of clonidine on glucose utilization. Amiloride antagonized the effects of clonidine on insulin secretion but did not enhance markedly glucose utilization in the presence or absence of clonidine. Carbamylcholine and arecoline reversed the effects of clonidine on glucose utilization and partly reversed the effects on insulin release in the absence of extracellular Ca²⁺. Prostaglandin (PG) E₂, but not PGF_2α, inhibited glucose utilization in a time- and concentration-dependent manner. PGE₂ also inhibited glucose-stimulated insulin release. Pertussis toxin blocked both actions of PGE₂. The cyclooxygenase inhibitor indomethacin did not affect insulin release or glucose utilization in the presence of clonidine. Thus, elevated intracellular Ca²⁺ levels antagonize the effects of clonidine on insulin release, whereas other mediators appear to be required to alter glucose utilization.