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 crucial 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 potassium chloride-induced insulin release. BDF 9148 had no effect on KATP 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 beta-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 beta-cell.
Wahl
M A
MA
Department of Pharmacology, Eberhard-Karls Universität Tübingen, Germany.
Anulukanapakorn
K
K
Ammon
H P
HP
D000818:Animals; D001384:Azetidines / Q000494:pharmacology*; D002132:Calcium Radioisotopes / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D012414:Rubidium Radioisotopes; D015222:Sodium Channels / Q000187:drug effects*; D012979:Sodium Radioisotopes; D014701:Veratridine / Q000494:pharmacology
D001384:Azetidines; D002132:Calcium Radioisotopes; D002316:Cardiotonic Agents; D007328:Insulin; D012414:Rubidium Radioisotopes; D015222:Sodium Channels; D012979:Sodium Radioisotopes; C071117:BDF 9148; D014701:Veratridine