pH-Dependence of Glucose-Dependent Activity of Beta Cell Networks in Acute Mouse Pancreatic Tissue Slice

Autor: Sandra Postić, Marko Gosak, Wen-Hao Tsai, Johannes Pfabe, Srdjan Sarikas, Andraž Stožer, Dean Korošak, Shi-Bing Yang, Marjan Slak Rupnik
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Frontiers in Endocrinology, Vol 13 (2022)
Druh dokumentu: article
ISSN: 1664-2392
DOI: 10.3389/fendo.2022.916688
Popis: 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.
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