Mechanisms of coordination of Ca2+ signals in pancreatic islet cells
Mechanisms of coordination of Ca2+ signals in pancreatic islet cells
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DOI：
10.2337/diabetes.48.10.1971
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发表时间：
1999-10-01
期刊：
影响因子：
7.7
通讯作者：
Grohovaz, F
中科院分区：
文献类型：
--
作者：
Bertuzzi, F;Davalli, AM;Grohovaz, F
在胰岛细胞内，细胞内钙离子浓度的节律性变化被报道为对刺激的葡萄糖浓度的反应，并与胰岛素的脉动性释放同步。我们探索了负责胰岛细胞内钙信号传播的可能机制，特别是缝隙连接通讯，这一途径被广泛认为是负责协调分泌活动的途径。利用Fura-2成像，我们发现在胰岛细胞中有多种机制控制着钙信号转导。18α-甘草次酸阻断缝隙连接极大地抑制了机械刺激引起的细胞内钙波的传播，但不影响细胞内钙信号和高糖引起的胰岛素分泌。在两种实验条件下，钙升高的来源也不同，第一种是由内库释放维持的，第二种是由硝苯地平敏感的钙内流维持的。此外，葡萄糖诱导的钙波能够通过无细胞裂隙传播，表明扩散因子可以控制钙信号的协调。我们的结果提供了证据，证明在β细胞中存在多种钙信号机制，细胞间的钙波传播或胰岛素分泌对葡萄糖的反应不需要缝隙连接。
Within pancreatic islet cells, rhythmic changes in the cytosolic Ca2+ concentration have been reported to occur in response to stimulatory glucose concentrations and to be synchronous with pulsatile release of insulin. We explored the possible mechanisms responsible for Ca2+ signal propagation within islet cells, with particular regard to gap junction communication, the pathway widely credited with being responsible for coordination of the secretory activity. Using fura-2 imaging, we found that multiple mechanisms control Ca2+ signaling in pancreatic islet cells. Gap junction blockade by 18 alpha-glycyrrhetinic acid greatly restricted the propagation of Ca2+ waves induced by mechanical stimulation of cells but affected neither Ca2+ signals nor insulin secretion elicited by glucose elevation. The source of Ca2+ elevation was also different under the two experimental conditions, the first being sustained by release from inner stores and the second by nifedipine-sensitive Ca2+ influx. Furthermore, glucose-induced Ca2+ waves were able to propagate across cell-free clefts, indicating that diffusible factors can control Ca2+ signal coordination. Our results provide evidence that multiple mechanisms of Ca2+ signaling operate in beta-cells and that gap junctions are not required for intercellular Ca2+ wave propagation or insulin secretion in response to glucose.