Henquin J C, Meissner H P
Biochem Pharmacol. 1982 Apr 1;31(7):1407-15. doi: 10.1016/0006-2952(82)90036-3.
The effects of tolbutamide and diazoxide on 86Rb+ fluxes, 45Ca2+ uptake, insulin release and B cell membrane potential have been studied in rat or mouse islets. In the presence of 3 mM glucose, tolbutamide rapidly and reversibly decreased Rb+ efflux from perifused islets and depolarised B cells. The effect on Rb+ efflux was paradoxically more marked with 20 than 100 micrograms/ml tolbutamide, at least in the presence of extracellular calcium. Addition of tolbutamide to a medium containing 6 mM glucose and calcium increased Rb+ efflux transiently with 20 micrograms/ml and permanently with 100 micrograms/ml. The drug also inhibited Rb+ influx in islet cells, but had little effect on Rb+ net uptake. Diazoxide rapidly, steadily and reversibly increased Rb+ efflux in a dose-dependent manner (20-100 micrograms/ml). When 20 micrograms/ml tolbutamide and diazoxide were combined in the presence of 3 mM glucose, only a slight decrease in Rb+ efflux was observed. The depolarisation of B cells normally produced by tolbutamide was markedly reduced and the electrical activity completely suppressed by diazoxide. In the presence of 10mM glucose, diazoxide increased Rb+ efflux from the islets and hyperpolarised B cells. Tolbutamide, tetraethylammonium and quinine reversed the increase in Rb+ efflux the inhibition of Ca2+ uptake and the suppression of insulin release produced by diazoxide. Tolbutamide rapidly reversed the hyperpolarisation and restored electrical activity. It is suggested that the stimulation and inhibition of insulin release by tolbutamide and diazoxide are due to their respective ability to decrease and to increase the K permeability of the B cell membrane. This change in K permeability leads either to depolarisation and stimulation of Ca2+ influx or to hyperpolarisation and inhibition of Ca2+ influx.
已在大鼠或小鼠胰岛中研究了甲苯磺丁脲和二氮嗪对⁸⁶Rb⁺通量、⁴⁵Ca²⁺摄取、胰岛素释放及B细胞膜电位的影响。在3 mM葡萄糖存在的情况下，甲苯磺丁脲能迅速且可逆地降低灌流胰岛的Rb⁺外流，并使B细胞去极化。至少在细胞外钙存在的情况下，20微克/毫升甲苯磺丁脲对Rb⁺外流的影响反常地比100微克/毫升时更显著。将甲苯磺丁脲添加到含6 mM葡萄糖和钙的培养基中，20微克/毫升时会使Rb⁺外流短暂增加，100微克/毫升时则会使其永久性增加。该药物还抑制胰岛细胞的Rb⁺内流，但对Rb⁺净摄取影响很小。二氮嗪能迅速、稳定且可逆地以剂量依赖方式（20 - 100微克/毫升）增加Rb⁺外流。当在3 mM葡萄糖存在的情况下将20微克/毫升甲苯磺丁脲和二氮嗪联合使用时，仅观察到Rb⁺外流略有减少。甲苯磺丁脲通常引起的B细胞去极化被二氮嗪显著减弱，且电活动被完全抑制。在10 mM葡萄糖存在的情况下，二氮嗪增加了胰岛的Rb⁺外流并使B细胞超极化。甲苯磺丁脲、四乙铵和奎宁可逆转二氮嗪所引起的Rb⁺外流增加、Ca²⁺摄取抑制及胰岛素释放抑制。甲苯磺丁脲能迅速逆转超极化并恢复电活动。提示甲苯磺丁脲和二氮嗪对胰岛素释放的刺激和抑制作用分别归因于它们各自降低和增加B细胞膜钾通透性的能力。钾通透性的这种变化要么导致去极化并刺激Ca²⁺内流，要么导致超极化并抑制Ca²⁺内流。
