Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Institute of Physiology, Faculty of Medicine, University of Maribor, Maribor, Slovenia.
Front Endocrinol (Lausanne). 2022 Jun 28;13:916688. doi: 10.3389/fendo.2022.916688. eCollection 2022.
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 Ca 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 Ca 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.
细胞外 pH 值有可能影响胰腺β细胞功能的各个方面。为了解释这种影响，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细胞外 pH 值对生理条件下葡萄糖依赖性β细胞激活和集体活动的影响。为此，我们使用小鼠胰腺组织切片来进行细胞质 Ca 振荡的高时间分辨率功能成像。我们研究了生理 H 过剩或耗竭对胰岛中β细胞的激活特性以及集体活动的影响。我们的结果表明，降低 pH 值会在亚刺激葡萄糖浓度下激活一部分β细胞，增强β细胞的平均活性，并改变胰岛中β细胞网络的特性。β细胞平均活性的增强是通过细胞质 Ca 成像间接确定的，而胰岛素分泌的直接测量则证实，这种增强的活性伴随着更高的胰岛素释放。此外，较低 pH 值下功能连接性降低和功能分离度增加，这都是细胞间通讯减少的迹象，但并不一定会导致胰岛素释放受损。
