Ionic mechanism of diphenylhydantoin action on glucose-induced insulin release.
Diphenylhydantoin inhibits glucose-stimulated insulin release. The mode of action of diphenylhydantoin was investigated by characterizing its effect on 86Rb and 45Ca fluxes in isolated pancreatic islets. The inhibition of glucose-stimulated insulin release by diphenylhydantoin was apparently not attributable to activation of a Na+ + K+ATPase as diphenylhydantoin failed to affect 86Rb net uptake, at least in glucose-stimulated islets. Diphenylhydantoin decreased 45Ca net uptake by the islets, an effect possibly due to inhibition of Ca2+ entry into the islet cells. Diphenylhydantoin indeed markedly inhibited the glucose-induced increase in 45Ca outflow and decreased the process of 40Ca-45 exchange evoked by a rise in extracellular Ca2+ concentration. Diphenylhydantoin failed to affect the inhibitory action of glucose upon 45Ca outflow whether in the presence or absence of extracellular Ca2+, and did not impair the antimycin A-induced release of 45Ca from intracellular organelles. These findings suggest that the inhibitory effect of diphenylhydantoin upon glucose-stimulated insulin release is attributable mainly to a blockade of Ca2+ inflow into the beta-cell.
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004789:Enzyme Activation; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats; D012413:Rubidium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D007328:Insulin; D010672:Phenytoin; D000968:Antimycin A; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D012413:Rubidium; D002118:Calcium