Activation of the Na+/K+-ATPase by insulin and glucose as a putative negative feedback mechanism in pancreatic beta-cells
Activation of the Na+/K+-ATPase by insulin and glucose as a putative negative feedback mechanism in pancreatic beta-cells
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DOI：
10.1007/s00424-008-0592-4
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发表时间：
2009-04-01
影响因子：
4.5
通讯作者：
Drews, G.
中科院分区：
文献类型：
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作者：
Duefer, M.;Haspel, D.;Drews, G.
磺酰脲受体1型敲除（SUR1(-/-)）小鼠的胰腺β细胞表现出振荡膜电位（V (m)），表明尽管缺乏K-ATP通道，超极化仍会发生。我们假设葡萄糖激活了Na+/K+- atp酶，从而增加了超极化电流。在SUR1(-/-) β细胞中葡萄糖升高导致V (m)和[Ca2+](c)的短暂下降，而不依赖于肌浆和内质网Ca2+激活的atp酶（SERCA）的激活。这不受K+通道阻断的影响，但被ATP耗尽和瓦巴因抑制。葡萄糖的增加也降低了[Na+](c)，乌阿因逆转了这一作用。外源性胰岛素降低[Na+](c)和超极化V (m)。抑制胰岛素信号在SUR1(-/-) β细胞钝化葡萄糖诱导的[Ca2+]的减少(c)。Tolbutamide （1 mmol/l）揭示了葡萄糖对野生型β细胞中[Ca2+](c)的serca独立作用。数据显示，在SUR1(-/-) β细胞中，葡萄糖可能通过增加[ATP]来激活Na+/K+-ATP酶(c)。胰岛素也能刺激泵，增强葡萄糖的作用。因此，涉及泵的途径可能作为某些代谢紊乱的潜在药物靶点。
Pancreatic beta-cells of sulfonylurea receptor type 1 knock-out (SUR1(-/-)) mice exhibit an oscillating membrane potential (V (m)) demonstrating that hyper-polarisation occurs despite the lack of K-ATP channels. We hypothesize that glucose activates the Na+/K+-ATPase thus increasing a hyper-polarising current. Elevating glucose in SUR1(-/-) beta-cells resulted in a transient fall in V (m) and [Ca2+](c) independent of sarcoplasmic and endoplasmic reticulum Ca2+-activated ATPase (SERCA) activation. This was not affected by K+ channel blockade but inhibited by ATP depletion and by ouabain. Increasing glucose also reduced [Na+](c), an effect reversed by ouabain. Exogenously applied insulin decreased [Na+](c) and hyper-polarised V (m). Inhibiting insulin signalling in SUR1(-/-) beta-cells blunted the glucose-induced decrease of [Ca2+](c). Tolbutamide (1 mmol/l) disclosed the SERCA-independent effect of glucose on [Ca2+](c) in wild-type beta-cells. The data show that in SUR1(-/-) beta-cells, glucose activates the Na+/K+-ATPase presumably by increasing [ATP](c). Insulin can also stimulate the pump and potentiate the effect of glucose. Pathways involving the pump may thus serve as potential drug targets in certain metabolic disorders.