α₂-adrenoceptor stimulation affects total glucose utilization in isolated islets of Langerhans

Glucose utilization in isolated islets of Langerhans of the rat was determined by measuring the conversion of [5-³H]glucose (10 mM) to ³H₂O. The α₂-adrenoceptor agonists clonidine, epinephrine, and norepinephrine in the presence of the α₁-adrenoceptor antagonist prazosin and the β-adrenoceptor antagonist propranolol inhibited glucose utilization by as much as 50%. Yohimbine, an α₂-adrenoceptor antagonist, reversed the reduction in glucose utilization evoked by α₂ receptor agonists. The cholinomimetics carbachol and muscarine, and 8-bromo-cyclic GMP, but not other cyclic nucleotides, reversed the clonidine-induced suppression of glucose utilization. 3-Isobutyl-1-methylxanthine potentiated the stimulation of glucose utilization by carbachol with clonidine. In contrast, the β-adrenoceptor agonist isoproterenol did not affect glucose utilization. Forskolin, which activates adenylate cyclase, reduced glucose utilization and did not affect the inhibitory response to clonidine. The ester phorbol 12,13-dibutyrate induced a latent reversal of the effects of clonidine. Insulin release paralleled changes in glucose utilization with α₂-adrenoceptor agonists. Carbachol and 8-bromo-cyclic GMP antagonized the α₂-adrenoceptor-induced inhibition of insulin release. During sustained insulin release (60 min), 8-bromo-cyclic AMP became a more potent modulator of secretion than 8-bromo-cyclic GMP in the presence of clonidine, although glucose utilization was not enhanced by 8-bromo-cyclic AMP.