RT Journal Article SR Electronic T1 β-cells operate collectively to help maintain glucose homeostasis JF bioRxiv FD Cold Spring Harbor Laboratory SP 765933 DO 10.1101/765933 A1 Boris Podobnik A1 Dean Korošak A1 Maša Skelin Klemen A1 Andraž Stožer A1 Jurij Dolenšek A1 Marjan Slak Rupnik A1 Plamen Ch. Ivanov A1 Petter Holme A1 Marko Jusup YR 2019 UL http://biorxiv.org/content/early/2019/12/01/765933.abstract AB Residing in the islets of Langerhans in the pancreas, beta cells contribute to glucose homeostasis by managing the body’s insulin supply. A circulating hypothesis has been that healthy beta cells heavily engage in cell-to-cell communication to perform their homeostatic function. We provide strong evidence in favor of this hypothesis in the form of (i) a dynamical network model that faithfully mimics fast calcium oscillations in response to above-threshold glucose stimulation and (ii) empirical data analysis that reveals a qualitative shift in the cross-correlation structure of measured signals below and above the threshold glucose concentration. Combined together, these results point to a glucose-induced transition in beta-cell activity thanks to increasing coordination through gap-junctional signaling and paracrine interactions. The model further suggests how the conservation of entire cell-cell conductance, observed in coupled but not uncoupled beta cells, emerges as a collective phenomenon. An overall implication is that improving the ability to monitor beta-cell signaling should offer means to better understand the pathogenesis of diabetes mellitus.