EFFECT OF A SODIUM-CHANNEL ACTIVATOR (BDF-9148) ON INSULIN-SECRETION IN MOUSE PANCREATIC-ISLETS

The interplay of the ion channels of the pancreatic beta-cell is a cru cial step in the regulation of insulin secretion. Though the presence of sodium channels is obvious in the pancreatic beta-cell, their role is not yet understood. Using a specific modulator of sodium channels, BDF 9148, a concentration - dependent reduction of glucose-stimulated insulin release was found. BDF 9148 also reduced tolbutamide- or potas sium chloride-induced insulin release. BDF 9148 had no effect on K-ATP channel function as estimated by Rb-86(+) efflux measurement and was also ineffective on Ca-45(2+) uptake but augmented Na-22(+) uptake. BD F 9148 did not alter the electrical activity of beta-cells significant ly. Since BDF 9148 antagonized the stimulatory effect of veratridine o n insulin release, sodium channels are likely to be the target of its action. In conclusion, the sodium-channel modulator BDF 9148 inhibits nutrient-induced insulin release by a mechanism which is not involved in the generation of action potentials in the beta-cell.