pH-Dependence of Glucose-Dependent Activity of Beta Cell Networks in Acute Mouse Pancreatic Tissue Slice.
pH-Dependence of Glucose-Dependent Activity of Beta Cell Networks in Acute Mouse Pancreatic Tissue Slice.
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DOI：
10.3389/fendo.2022.916688
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发表时间：
2022
影响因子：
5.2
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中科院分区：
文献类型：
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细胞外pH值有可能影响胰腺β细胞功能的各个方面。为了解释这种效应，提出了许多涉及细胞外和细胞内靶点和途径的机制。在这里，我们专注于重新评估在生理条件下细胞外pH值对葡萄糖依赖性β细胞活化和集体活动的影响。为此，我们采用小鼠胰腺组织切片进行高时间分辨功能成像的胞质钙离子振荡。我们研究了生理H+过量或耗尽对胰岛中β细胞的激活特性以及集体活性的影响。我们的研究结果表明，降低pH值调用亚刺激葡萄糖浓度的β细胞的一个子集的激活，增强β细胞的平均活性，并改变β细胞网络特性在胰岛。β细胞的增强的平均活性是利用胞质Ca 2+成像间接测定的，而胰岛素分泌的直接测量证实了这种增强的活性伴随着更高的胰岛素释放。此外，在较低pH值下功能连接性降低和功能分离较高（这两种信号都是细胞间通讯减少的标志）不一定导致胰岛素释放受损。
Extracellular pH has the potential to affect various aspects of the pancreatic beta cell function. To explain this effect, a number of mechanisms was proposed involving both extracellular and intracellular targets and pathways. Here, we focus on reassessing the influence of extracellular pH on glucose-dependent beta cell activation and collective activity in physiological conditions. To this end we employed mouse pancreatic tissue slices to perform high-temporally resolved functional imaging of cytosolic Ca2+ oscillations. We investigated the effect of either physiological H+ excess or depletion on the activation properties as well as on the collective activity of beta cell in an islet. Our results indicate that lowered pH invokes activation of a subset of beta cells in substimulatory glucose concentrations, enhances the average activity of beta cells, and alters the beta cell network properties in an islet. The enhanced average activity of beta cells was determined indirectly utilizing cytosolic Ca2+ imaging, while direct measuring of insulin secretion confirmed that this enhanced activity is accompanied by a higher insulin release. Furthermore, reduced functional connectivity and higher functional segregation at lower pH, both signs of a reduced intercellular communication, do not necessary result in an impaired insulin release.