Functional architecture of pancreatic islets identifies a population of first responder cells that drive the first-phase calcium response

• DOI: 10.1371/journal.pbio.3001761
• Publication Date: 2022-09-13T17:44:46Z
• Authors: Vira Kravets; JaeAnn M. Dwulet; Wolfgang E. Schle...; David J. Hodson; Anna M. Davis; Laura Pyle; Robert A. Piscopio; Maura Sticco-Ivins; Richard K. P. Ben...
• Keywords: Pancreatic Islets; First responder

Insulin-secreting β-cells are functionally heterogeneous. Whether there exist cells driving the first-phase calcium response in individual islets, has not been examined. We examine "first responder" cells, defined by earliest [Ca2+] during elevation, distinct from previously identified "hub" and "leader" cells. used islets isolated Mip-CreER; Rosa-Stop-Lox-Stop-GCamP6s mice (β-GCamP6s) that show β-cell-specific GCamP6s expression following tamoxifen-induced CreER-mediated recombination. First responder showed characteristics of high membrane excitability lower electrical coupling to their neighbors. The time islet was spatially organized, dependent on cell's distance first cell, consistent over up approximately 24 h. When were laser ablated, slowed down, diminished, discoordinated compared random cell ablation. Cells next respond often took role upon In summary, we discover characterize a β-cell state, critical for glucose.