Effects of neurotoxins on pancreatic islets: Elucidation of a possible role for sodium channels in the secretory response

Abstract

The neurotoxins veratridine and Leiurus toxin were used to characterize the nature of the sodium channel in the pancreatic β-cell membrane in relation to metabolc and secretory events. Insulin release and glycolytic flux were measured on batch-incubated rat islets. Veratridine, 200 μM, but not 10 μM, elicited a secretory response in the presence of 5.6 mM (basal) glucose, but did not influence the response to 15.3 mM glucose. Leiurus toxin, 20 nM, together with basal glucose and 10 μM veratridine induced insulin release, although Leiurus toxin, alone, was not effective. The secretory responses to the neurotoxins, but not 15.3 mM glucose, were blocked by tetrodotoxin. Glucose utilization was enhanced by 200 μM veratridine in the presence of basal glucose. Leiurus toxin at 20 nM increased the glycolytic rate which was further enhanced by the addition of 10 μM veratridine. The increments in glycolytic flux were partially or completely blocked by tetrodotoxin. Ouabain, 1.0 mM, had no effect on the secretory response to veratridine, but completely blocked the veratridine-induced increase in glycolytic flux. These observations indicate that the sodium channels in the β-cell membrane are pharmacologically similar to those in neuronal plasma membranes. Furthermore, the secretory response elicited by neurotoxins may occur independently of an increase in glycolytic flux. The major role of glycolytic flux may be to provide energy for extrusion of sodium from the β-cell.