Li Xian-Tao, Yun Meng-Ze
School of Medicine, Jingchu University of Technology, Jingmen, China.
Front Cell Dev Biol. 2025 Jun 23;13:1528369. doi: 10.3389/fcell.2025.1528369. eCollection 2025.
The oral hypoglycemic drug sulfonylureas exhibit substantial therapeutic benefits for millions of patients with type 2 diabetes mellitus (T2DM), although with common adverse effects, such as hypoglycemia. It is generally believed that inhibition of K channels by sulfonylureas in pancreatic β-cells enables the insulin release to reduce glycemic levels, a primary mechanism underlying pharmacological effectiveness. Accumulated evidence reveals that multiple ion channels, such as Kv and TRP, are also expressed in β-cells in the pancreatic islets of Langerhans, and these channels, particularly Kv2.1, show important functional roles in tuning the electrical activity of β-cells, accordingly participating in the modulation of insulin secretion. Existing data reveal that several ion channels besides K channels could be directly blocked by sulfonylureas, and consequent membrane depolarization serves to facilitate the insulin release, possibly contributing to glycemic control or side effects. Furthermore, the modulation of sulfonylurea-mediated activation of Epac2A on diverse ion channels could produce the pharmacological efficacy, indicative of an indirect regulatory way. The scenario of sulfonylureas impacting diverse ion channels may provide an alternative explanation for the antidiabetic actions and side effects, extending our understanding of these classical clinic drugs.
口服降糖药磺脲类药物对数百万2型糖尿病（T2DM）患者具有显著的治疗益处，尽管存在低血糖等常见不良反应。一般认为，磺脲类药物在胰腺β细胞中抑制钾通道可使胰岛素释放，从而降低血糖水平，这是其药理作用的主要机制。越来越多的证据表明，多种离子通道，如Kv和TRP，也在胰岛的β细胞中表达，这些通道，特别是Kv2.1，在调节β细胞的电活动中发挥重要作用，从而参与胰岛素分泌的调节。现有数据表明，除钾通道外，几种离子通道也可被磺脲类药物直接阻断，由此产生的膜去极化有助于促进胰岛素释放，这可能与血糖控制或副作用有关。此外，磺脲类药物介导的Epac2A对多种离子通道的激活调节可能产生药理作用，这表明存在一种间接调节方式。磺脲类药物影响多种离子通道的情况可能为其抗糖尿病作用和副作用提供另一种解释，从而扩展我们对这些经典临床药物的理解。
