Glucose stimulates voltage- and calcium-dependent inositol trisphosphate production and intracellular calcium mobilization in insulin-secreting beta TC3 cells
Glucose stimulates voltage- and calcium-dependent inositol trisphosphate production and intracellular calcium mobilization in insulin-secreting beta TC3 cells
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DOI：
10.1042/bj3140339
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发表时间：
1996-02-15
影响因子：
4.1
通讯作者：
Dissing, S
中科院分区：
文献类型：
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作者：
Gromada, J;FrokjaerJensen, J;Dissing, S
在胰岛素分泌β TC 3细胞中研究了葡萄糖刺激和Kt去极化后导致细胞内游离Ca 2+浓度（[Ca 2 +]（i））升高的细胞过程。用11.2 mM葡萄糖刺激导致肌醇1，4，5-三磷酸产生和从细胞内储存释放Ca 2+。在Ins（1，4，5）P-3浓度的变化和[Ca 2 +]（i）的升高之间观察到强相关性，与前一种化合物负责从细胞内储存释放Ca 2+一致。当通过用Ca 2+螯合剂1，2-双（2-氨基苯氧基）乙烷-NNN ′ N ′-四乙酸（BAPTA）加载细胞而在葡萄糖刺激下保持低[Ca 2 +]（i）时，Ins（1，4，5）P-3产量的增加降低了68 +/-4%。Ins（1，4，5）P-3的合成在ATP敏感性K+通道开放剂二氮嗪（diazoxide）的超极化作用下被抑制，这与膜电位控制Ins（1，4，5）P-3的合成速率是一致的。去极化K+浓度在细胞外Ca ~（2+）存在和不存在的情况下均引起[Ca ~（2+）]（i）和Ins（1，4，5）P-3产生的变化，并且从细胞外K+浓度与膜电位之间的关系中，我们发现半最大Ins（1，4，5）通过从-56 mV的静息电位28 mV去极化和通过390 nM的[Ca 2 +]（i）升高产生P-3。我们的结论是，刺激诱导的膜电位和[Ca 2 +]（i）的变化是重要的，在控制胰岛素（1，4，5）P-3的生产在β TC-3细胞和葡萄糖刺激的Ca 2+动员从细胞内存储是由于电压依赖性的胰岛素（1，4，5）P-3的生产，并取决于同时增加[Ca 2 +]（i）。
The cellular processes leading to a rise in the intracellular free Ca2+ concentration ([Ca2+](i)) after glucose stimulation and Kt depolarization were investigated in insulin-secreting beta TC3 cells. Stimulation with 11.2 mM glucose causes inositol 1,4,5-trisphosphate production and release of Ca2+ from intracellular stores. A strong correlation was observed between the changes in Ins(1,4,5)P-3 concentration and the rise in [Ca2+](i), consistent with the former compound being responsible for release of Ca2+ from intracellular stores. The increase in Ins(1,4,5)P-3 production was reduced by 68 +/- 4% when [Ca2+](i) was kept low on glucose stimulation by loading cells with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-NNN'N'-tetra- acetic acid (BAPTA). The Ins(1,4,5)P-3 production was prevented in cells hyperpolarized with diazoxide, an opener of ATP-sensitive K+-channels, consistent with the membrane potential controlling the rate of Ins(1,4,5)P-3 synthesis. Depolarizing K+ concentrations evoked changes in [Ca2+](i) and Ins(1,4,5)P-3 production in both the presence and the absence of extracellular Ca2+, and from the relation between the extracellular K+ concentration and membrane potential we found a half-maximal Ins(1,4,5)P-3 production by a 28 mV depolarization from a resting potential of -56 mV and by a rise in [Ca2+](i) of 390 nM. We conclude that stimulation-induced changes in membrane potential and [Ca2+](i) are important in controlling Ins(1,4,5)P-3 production in beta TC-3 cells and that glucose-stimulated Ca2+ mobilization from intracellular stores is due to voltage-dependent Ins(1,4,5)P-3 production and depends on the concurrent increase in [Ca2+](i).