Smits P, Thien T
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Diabetologia. 1995 Jan;38(1):116-21. doi: 10.1007/BF02369361.
Sulphonylurea derivatives are widely used in the treatment of non-insulin-dependent diabetes mellitus. The mechanism of action of the insulino-tropic effect of these agents is based on the closure of adenosine-5'-triphosphate (ATP)-sensitive potassium channels (KATP-channels) in the beta cells of the pancreas. In the last decade, these KATP-channels have been demonstrated in myocardial cells as well as in vascular smooth muscle cells. During myocardial ischaemia, the KATP-channels are thought to open by a fall in the cytosolic ATP concentration. The increase in the extracellular adenosine concentration, and the release of endothelium-derived hyperpolarizing factor (EDHF) during ischaemia may further contribute to the opening of cardiovascular KATP-channels. Independently from the mechanism of opening, sulphonylurea derivatives have been reported to block the opening of cardiovascular KATP-channels. Related to the role of KATP-channel-opening in the (patho)physiology of ischaemia, the use of sulphonylurea derivatives significantly modifies the outcome of experimental myocardial infarction. Sulphonylurea derivatives impair the recovery of the contractile function and increase the ultimate infarct size in animal models. In contrast, sulphonylurea derivatives have a beneficial effect on the incidence of ventricular fibrillation as occurs after ischaemic incidents of the myocardium. Based on these experimental observations, human studies are indicated to investigate whether the use of these drugs modifies the clinical outcome of cardiovascular events in patients with non-insulin dependent diabetes mellitus.
磺酰脲类衍生物广泛用于治疗非胰岛素依赖型糖尿病。这些药物促胰岛素分泌作用的机制基于胰腺β细胞中三磷酸腺苷（ATP）敏感性钾通道（KATP通道）的关闭。在过去十年中，已在心肌细胞以及血管平滑肌细胞中证实了这些KATP通道。在心肌缺血期间，KATP通道被认为会因细胞溶质ATP浓度下降而开放。细胞外腺苷浓度的增加以及缺血期间内皮衍生超极化因子（EDHF）的释放可能进一步促使心血管KATP通道开放。与开放机制无关，据报道磺酰脲类衍生物可阻断心血管KATP通道的开放。鉴于KATP通道开放在缺血（病理）生理学中的作用，磺酰脲类衍生物的使用显著改变了实验性心肌梗死的结果。在动物模型中，磺酰脲类衍生物会损害收缩功能的恢复并增加最终梗死面积。相比之下，磺酰脲类衍生物对心肌缺血事件后发生的心室颤动发生率具有有益作用。基于这些实验观察结果，有必要开展人体研究以调查使用这些药物是否会改变非胰岛素依赖型糖尿病患者心血管事件的临床结局。
