Hellman B
Acta Biol Med Ger. 1982;41(12):1211-9.
The mechanisms for sulfonylurea stimulation of insulin release were explored by studying how these compounds interacted with beta-cell-rich pancreatic islets isolated from ob/ob-mice. Although sulfonylureas from the "second generation" were taken up to a greater extent, there was no direct correlation between the binding to the islets and the stimulation of insulin release. Drugs, which are known to augment the hypoglycemic action of the sulfonylureas, displaced these compounds from serum albumin to the islets. Sulfonylurea binding to the beta-cells is supposed to result from a hydrophobic interaction of the drug with the beta-cell surface counteracted by electrostatic repulsion from fixed negative charges at the cell surface. Like glucose, the sulfonylureas stimulate insulin release by promoting the Ca2+ influx into the beta-cells. The enhanced Ca2+ influx cannot be accounted for by Ca2+-ionophoretic activity but is secondary to a depolarisation of the beta-cells by a mechanism which may involve a reaction with thiol groups in the plasma membrane.
通过研究这些化合物如何与从ob/ob小鼠分离出的富含β细胞的胰岛相互作用，探索了磺脲类药物刺激胰岛素释放的机制。尽管“第二代”磺脲类药物的摄取程度更高，但与胰岛的结合和胰岛素释放的刺激之间没有直接相关性。已知能增强磺脲类药物降血糖作用的药物，将这些化合物从血清白蛋白置换到胰岛。磺脲类药物与β细胞的结合被认为是药物与β细胞表面的疏水相互作用，这种相互作用被细胞表面固定负电荷的静电排斥所抵消。与葡萄糖一样，磺脲类药物通过促进Ca2+流入β细胞来刺激胰岛素释放。Ca2+流入增加不能用Ca2+离子载体活性来解释，而是继发于β细胞的去极化，其机制可能涉及与质膜中巯基的反应。
