[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 micrograms/ml) produced a significant increase in the immunoreactive insulin (IRI) level in the perfusate. The Diso-induced 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 micrograms/0.1 ml) under the perfusion of Krebs-Ringer bicarbonate buffer solution containing 0.3% glucose (0.3% glucose buffer), but not under the perfusion of Krebs-Ringer bicarbonate buffer solution containing 0.1% glucose (0.1% glucose buffer). The Diso-induced 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%, 0.2 ml) under the perfusion of 0.1% glucose buffer, but not under the perfusion of 0.3% glucose buffer. Furthermore, Diso also suppressed the hypersecretion of insulin induced by increasing the glucose concentration from 0.1% to 0.3% in the perfusion fluid. The suppressing action of Diso on glucose-stimulated 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.