Sp-5,6-dichloro-1-βd-ribofuranosylbenzimidazole-3'5'cyclic monophosphorothioate is a potent stimulus for insulin release

The Sp-isomer of 5,6-dichloro-1-βD-ribofuranosylbenz-imidazole-3'5'cyclic monophosphorothioate (Sp-5,6-DCl-cBIMPS) at micromolar concentrations was a more potent stimulus for insulin release than 8-bromo-cyclic (c) AMP in isolated pancreatic islets of the rat. Sp-5,6-DCl-cBIMPS increased basal secretion, and potentiated glucose-stimulated insulin release to levels similar to those evoked by glucagon. A ten-fold higher concentration of 8-bromo-cAMP was required to mimic the potentiating effects of Sp-5,6-DCl-cBIMPS. Neither 8-para-chlorophenylthio-cGMP, 8-bromo-cGMP, nor dibutyryl-cGMP affected insulin release. Thus, Sp-5,6-DCl-cBIMPS is a potent and specific stimulus for cAMP-mediated insulin release.