磺脲类降糖药主要通过刺激胰岛β细胞释放胰岛素而降低血糖,但近来发现长期治疗过程中部分磺脲类药物还具有非胰岛素依赖的降糖机制。一方面磺脲类药可激活细胞内特异的蛋白磷酸化酶而促进葡萄糖转运子4/1的转位,激活糖原合成酶,降低糖原合成酶激酶-3活性,从而促进外周组织的葡萄糖利用。另一方面,部分磺脲类药特别是格列美脲分子可直接插入脂肪细胞/肌细胞膜上的吞饮小泡/不溶于去污剂的富含糖脂筏(caveolae/DIGs区),激活后者的非受体酪氨酸激酶pp59Lyn,进而使胰岛素受体底物-1酪氨酸磷酸化,发动代谢性的拟胰岛素信号级联反应。 Sulfonylurea hypoglycemic agents lower blood glucose mainly by stimulating islet-derived beta cells to release insulin, but it has recently been found that some sulfonylureas also have a non-insulin-dependent hypoglycemic mechanism during long-term treatment. On the one hand sulfonylurea drugs can activate intracellular specific protein phosphorylase and promote glucose transporter 4/1 translocation, activate glycogen synthase, reduce glycogen synthase kinase-3 activity, thereby promoting the peripheral tissues of glucose use. On the other hand, some sulfonylureas, especially glimepiride, can be directly inserted into fat-absorbing / vesicle-insoluble / detergent-insoluble lipidolabile (caveolae / DIGs) regions of the adipocyte / myocyte membrane to activate The latter non-receptor tyrosine kinase pp59Lyn, which in turn phosphorylates the insulin receptor substrate-1 tyrosine, initiates a metabolic quasi- insulin signaling cascade.