Effect of a sodium-channel activator (BDF 9148) on insulin secretion in mouse pancreatic islets

Abstract

The interplay of the ion channels of the pancreatic β-cell is a crucial step in the regulation of insulin secretion. Though the presence of sodium channels is obvious in the pancreatic β-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 potassium chloride-induced insulin release. BDF 9148 had no effect on K_ATP channel function as estimated by ⁸⁶Rb⁺ efflux measurement and was also ineffective on ⁴⁵Ca²⁺ uptake but augmented ²²Na⁺ uptake. BDF 9148 did not alter the electrical activity of β-cells significantly. Since BDF 9148 antagonized the stimulatory effect of veratridine on 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 β-cell.