Calcium-antagonists and islet function. IV. Effect of D600.

D600 (2 to 20 muM; alpha-isopropyl-alpha [(N-methyl-N-homoveratril)-gamma-aminopropyl]-3,4,5-trimethoxyphenyl-acetonitril) caused a dose-related, rapid and reversible inhibition of glucose-induced insulin release. It also suppressed the insulinotropic action of a sulphonylurea but failed to affect the enhancing action of theophylline upon glucose-induced release. The inhibitory effect of D600 was enhanced at low extracellular Ca2+ concentration. D600 reduced both basal and glucose-stimulated 45calcium net uptake, whilst failing to affect the efflux of 45calcium from perifused islets. The recognition of glucose by the B-cell was also unaffected by D600 as judged by the effect of the sugar upon both 45calcium efflux and net uptake in the isolated islets. These findings are compatible with the hypothesis that the primary mode of action of D600 is to inhibit Ca2+ entry in the B-cell.