磺脲类药物对胰岛β细胞凋亡影响的研究进展

Progress about the effects of sulfonylureas on islet β cells apoptosis

磺脲类降糖药物目前广泛应用于2型糖尿病的临床治疗。它主要的降糖机制是通过与胰岛细胞膜上的磺脲类受体结合,关闭了由SUR1和KIR6.2组成的钾通道(KATP),导致了细胞膜的去极化,触发了L型钙离子通道开放,从而使钙离子大量内流,促进了胰岛细胞分泌胰岛素。但与此同时,大量钙离子内流,造成了胰岛细胞的钙超载,加之胰岛细胞活化过程中产生的大量氧自由基都造成了胰岛细胞的损伤。故很多文献报道,磺脲类药物对胰岛细胞有诱导凋亡作用,但机制各有不同。事实上,不同的磺脲类药物对于胰岛β细胞凋亡的作用机制尚未完全明确,且有很多争论。新近研究表明,一些新型磺脲类药物剂型,如格列美脲对胰岛细胞凋亡的作用可能有所不同。

Antidiabetic sulfonylureas is widely used in clinical therapy of type 2 diabetes recently. The effects are mainly mediated by closure of ATP-sensitive K ＋ （ KATP） channels after binding of sulfonylureas to their receptor, SURI, which is a constitutive part of the KATP channel as well as KIR6. 2. This results in membrane depolarization that culminates in Ca^2＋ entry through voltage-gated L-type Ca^2＋ channels and the onset of Ca^2＋ - dependent insulin release. But at the same time, too much calcium coming into the cells will induce the overloaded calcium. High concentration of reactive oxygen species were produced during the activation of islet beta ceils. The overloaded ealcium and excessive reactive oxygen species will hurt and induce the apoptosis of islet cells. A number of reports declared that sulfonylureas have effects on apoptosis of islet cells, but they have different mechanisms. In fact, the mechanism of different kinds of sulfonylurea＇s effect on islet cells apoptosis has not been elucidated. There still have many debates about it. Recent researches have showed that new formulation of sulfonylurea, such as glimepiride, may have different effect on islet cells apoptosis.