β Cells Operate Collectively to Help Maintain Glucose Homeostasis

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.