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- W4387338181 abstract "Orchestrated islet α-, β-, and δ-cell functions, and the ensuing regulated release of glucagon, insulin, and somatostatin, respectively, play critical roles in maintaining body euglycemia. Since hormone secretion of these cells are triggered by changes in the cytosolic calcium concentration ([Ca2+]C), tracking temporal dynamics of α-, β-, δ-cells [Ca2+]C would offer valuable readouts of their cellular functions. We employed in situ multicellular [Ca2+]C dynamic imaging simultaneously tracking Ca2+ signals emanating from Calbryte 590AM–loaded α-, β-, and δ-cells within fresh pancreas tissue slices of Ins1-Cre:GCaMP6fLoxP mice. Subsequently, live-cell time-lapse recordings were analyzed with custom-made Python scripts, and the recorded pancreas slices were post-hoc immunoassayed for glucagon and somatostatin to correlate cellular functions and the islet topological locations of α- and δ-cells, provided β-cells express the fluorescent Ca2+ sensor GCaMPf. This combined approach enables extraction of temporal [Ca2+]C dynamic changes within every islet cell type and permits large-scale network analyses, thereby revealing mechanistical interactions between α-, β-, and δ-cells. Our preliminary result suggests that Exendin-4 (Ex-4) at physiological concentration (0.2 mM) potentiates β-cells [Ca2+]C response to 9 mM glucose (HG) stimulation in a more responsive and longer-lasting fashion, whereas Ex-4 at 3.6 mM glucose (LG) only elevated globally the baseline [Ca2+]C in islets but did not trigger [Ca2+]C waveform propagation. Network analysis revealed higher mean degree cellular connectivity and clustering coefficient between β-cells in HG+Ex-4 conditions. α-cells [Ca2+]C activity are high at LG, decreased at HG condition, and were further reduced upon Ex-4 stimulation. δ-like-cells showed increased [Ca2+]C activities from LG to HG, but are blunted after Ex-4 addition. These initial findings supported our previous report that the gut-derived incretin serve to amplify insulin release by recruiting a highly coordinated subnetwork of β-cells. We further show here that the β-cell incretin potentiation at HG was reinforced by blunted α- and δ-like-cells [Ca2+]C response." @default.
- W4387338181 created "2023-10-05" @default.
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- W4387338181 date "2023-10-01" @default.
- W4387338181 modified "2023-10-06" @default.
- W4387338181 title "SIMULTANEOUS HIGH SPATIOTEMPORAL RESOLUTION CALCIUM DYNAMIC IMAGING ON ISLET A-, B-, D-CELLS WITHIN PANCREAS TISSUE SLICES UNCOVERS MECHANISMS OF INTRA-ISLET CELLULAR COMMUNICATION" @default.
- W4387338181 doi "https://doi.org/10.1016/j.cjca.2023.06.251" @default.
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