Alpha 2-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 alpha 2-adrenoceptor agonists clonidine, epinephrine, and norepinephrine in the presence of the alpha 1-adrenoceptor antagonist prazosin and the beta-adrenoceptor antagonist propranolol inhibited glucose utilization by as much as 50%. Yohimbine, an alpha 2-adrenoceptor antagonist, reversed the reduction in glucose utilization evoked by alpha 2 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 beta-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 alpha 2-adrenoceptor agonists. Carbachol and 8-bromo-cyclic GMP antagonized the alpha 2-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.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000294:innervation / Q000378:metabolism*; D008297:Male; D009712:Nucleotides, Cyclic / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D007328:Insulin; D009712:Nucleotides, Cyclic; D010703:Phorbol Esters; D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine