studies on the mechanisms of action of disopyramide on insulin secretion the modification by high glucose solution using the islet perifusion preparation and the isolated rat pancreas in situ perfusion preparation the effects of disopyramide diso on insulin secretion were studied in an isolated pancreatic islet perifusion experiment diso 300 microgramsml produced a significant increase in the immunoreactive insulin iri level in the perfusate the disoinduced iri rise was not affected by pretreatment with various autonomic blocking agents such as propranolol phentolamine or atropine in an isolated rat pancreas in situ perfusion experiment the iri level in the perfusate increased significantly after the administration of diso 300 micrograms01 ml under the perfusion of krebsringer bicarbonate buffer solution containing 03 glucose 03 glucose buffer but not under the perfusion of krebsringer bicarbonate buffer solution containing 01 glucose 01 glucose buffer the disoinduced iri rise was not affected by pretreatment with the autonomic blocking agents diso suppressed the iri rise which was induced by additional glucose application 25 02 ml under the perfusion of 01 glucose buffer but not under the perfusion of 03 glucose buffer furthermore diso also suppressed the hypersecretion of insulin induced by increasing the glucose concentration from 01 to 03 in the perfusion fluid the suppressing action of diso on glucosestimulated insulin secretion was partially recovered after pretreatment with propranolol or phentolamine these findings show that diso has both stimulatory and inhibitory effects on insulin secretion processes and that the inhibitory action of diso is suppressed by high glucose solution