Oxidative stress increases potassium efflux from pancreatic islets by depletion of intracellular calcium stores
Oxidative stress increases potassium efflux from pancreatic islets by depletion of intracellular calcium stores
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DOI：
10.1080/10715760000301051
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发表时间：
2000-01-01
影响因子：
3.3
通讯作者：
Ammon, HPT
中科院分区：
文献类型：
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作者：
Hennige, AM;Lembert, N;Ammon, HPT
对B细胞的氧化应激被认为与B细胞功能下降和B细胞破坏过程相关。在其他组织中，包括心脏、脑和肝脏，氧化应激已被证明可升高细胞内游离钙浓度并引起钾外流。我们使用巯基氧化剂DIP和BuOOH研究了氧化应激对胰岛Ca 2+和K+（Rb+）流出的影响。在3和16.7 mmol/l葡萄糖存在下，两种化合物均可逆地增加Rb-86（+）流出。Rb-86（+）外排的刺激在无钙时也很明显。DIP诱发的Ca-45（2+）从胰岛中的存在或不存在的细胞外钙的释放。使用钙激活钾通道（K-Ca）和高电导K+通道（BKCa）抑制剂，DIP对Rb-86（+）流出的影响略有减弱。在DIP存在下，甲苯磺丁脲对Rb-86（+）外排无影响。另一方面，一种内质网Ca ~（2+）-ATP酶的阻断剂毒胡萝卜素完全抑制DIP介导的Rb-86（+）外流。这些数据表明，巯基氧化剂诱导的钾从胰岛流出主要是通过释放细胞内钙和随后的刺激钙激活的钾流出介导的。
Oxidative stress to B-cells is thought to be of relevance in declining B-cell function and in the process of B-cell destruction. In other tissues including heart, brain and liver, oxidative stress has been shown to elevate the intracellular free calcium concentration and to provoke potassium efflux. We studied the effect of oxidative stress on Ca2+ and K+ (Rb+) outflow from pancreatic islets using the thiol oxidants DIP and BuOOH. Both compounds reversibly increased Rb-86(+) efflux in the presence of 3 and 16.7 mmol/l glucose. Stimulation of Rb-86(+) efflux was also evident in the absence of calcium. DIP evoked release of Ca-45(2+) from the pancreatic islets both in the presence or absence of extracellular calcium. Employing inhibitors of the calcium-activated potassium channel (K-Ca) and the high conductance K+-channel (BKCa), the effect of DIP on Rb-86(+) efflux was slightly diminished. Tolbutamide had no effect on Rb-86(+) efflux in the presence of DIP. On the other hand thapsigargin, a blocker of the Ca2+-ATPase of the endoplasmic reticulum, completely suppressed the DIP-mediated Rb-86(+) outflow. The data suggest that thiol oxidant-induced potassium efflux from pancreatic islets is mainly mediated through liberation of intracellular calcium and subsequent stimulation of calcium-activated potassium efflux.