Wahl M A, Koopmann I, Ammon H P
Department of Pharmacology, Institute of Pharmaceutical Sciences, Eberhard-Karls-University, Tübingen, Germany.
Exp Clin Endocrinol Diabetes. 1998;106(3):173-7. doi: 10.1055/s-0029-1211972.
Generation of free radicals and oxidative stress play a role in the development of islet dysfunction in diabetes. These mechanisms are known to affect membrane potential and cytosolic calcium in other cell types. The effect of oxidative stress, caused by tert-butyl-hydroperoxide (BuOOH), was therefore studied with respect to the redox ratio of glutathione, membrane potential, cytosolic calcium and insulin release in the insulin-secreting RINm5F cell. In RINm5F cells BuOOH decreased the redox ratio of glutathione and caused depolarization. This was associated with an increase in cytosolic calcium and insulin secretion. The effects of BuOOH on cytosolic calcium and insulin release were abolished in the absence of extracellular calcium and decreased by the calcium channel blocker verapamil. Our data suggest that in RINm5F cells oxidative stress causes insulin release by depolarization and subsequent calcium entry through voltage-dependent calcium channels.
自由基的产生和氧化应激在糖尿病胰岛功能障碍的发展中起作用。已知这些机制会影响其他细胞类型的膜电位和细胞溶质钙。因此，研究了叔丁基过氧化氢（BuOOH）引起的氧化应激对胰岛素分泌型RINm5F细胞中谷胱甘肽的氧化还原比、膜电位、细胞溶质钙和胰岛素释放的影响。在RINm5F细胞中，BuOOH降低了谷胱甘肽的氧化还原比并导致去极化。这与细胞溶质钙增加和胰岛素分泌有关。在没有细胞外钙的情况下，BuOOH对细胞溶质钙和胰岛素释放的影响被消除，并且钙通道阻滞剂维拉帕米使其降低。我们的数据表明，在RINm5F细胞中，氧化应激通过去极化和随后通过电压依赖性钙通道的钙内流导致胰岛素释放。
