Critical transitions in pancreatic islets.

Calcium signals in pancreatic β cell collectives show a sharp transition from uncorrelated to correlated state resembling a phase transition as the slowly increasing glucose concentration crosses the tipping point. However, the exact nature or the order of this phase transition is not well understood. Using confocal microscopy to record the collective calcium activation of β cells in an intact islet under changing glucose concentration in an increasing and then decreasing way, we first show that in, addition to the sharp transition, the coordinated calcium response exhibits a hysteresis indicating a critical, first-order transition. A network model of β cells combining link selection and coordination mechanisms capture the observed hysteresis loop and the critical nature of the transition. Our results point towards an understanding of the role of islets as tipping elements in the pancreas that, interconnected by perfusion, diffusion, and innervation, cause the tipping dynamics and abrupt insulin release.