β Cells Operate Collectively to Help Maintain Glucose Homeostasis
Boris Podobnik, Dean Korošak, Maša Skelin Klemen, Andraž Stožer, Jurij Dolenšek, Marjan Slak Rupnik, Plamen Ch. Ivanov, Petter Holme and Marko Jusup.
Biophysical Journal, DOI: https://doi.org/10.1016/j.bpj.2020.04.005
Residing in the islets of Langerhans in the pancreas, β cells contribute to glucose homeostasis by managing the body’s insulin supply. Although it has been acknowledged that healthy β cells engage in heavy cell-to-cell communication to perform their homeostatic function, the exact role and effects of such communication remain partly understood. We offer a novel, to our knowledge, perspective on the subject in the form of 1) a dynamical network model that faithfully mimics fast calcium oscillations in response to above-threshold glucose stimulation and 2) 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 β-cell activity thanks to increasing coordination through gap-junctional signaling and paracrine interactions. Our data and the model further suggest how the conservation of entire cell-cell conductance, observed in coupled but not uncoupled β cells, emerges as a collective phenomenon. An overall implication is that improving the ability to monitor β-cell signaling should offer means to better understand the pathogenesis of diabetes mellitus.