Collective Sensing of β-Cells Generates the Metabolic Code

Major part of a pancreatic islet is composed of $\beta$-cells that secrete insulin, a key hormone regulating influx of nutrients into all cells in a vertebrate organism to support nutrition, housekeeping or energy storage. $\beta$-cells constantly communicate with each other using both direct, short-range interactions through gap junctions, and paracrine long-range signaling. However, how these cell interactions shape collective sensing and cell behavior in islets that leads to insulin release is unknown. When stimulated by specific ligands, primarily glucose, $\beta$-cells collectively respond with expression of a series of transient Ca$^{2+}$ changes on several temporal scales. Here we reanalyze a set of Ca$^{2+}$ spike trains recorded in acute rodent pancreatic tissue slice under physiological conditions. We found strongly correlated states of co-spiking cells coexisting with mostly weak pairwise correlations widespread across the islet. Furthermore, the collective Ca$^{2+}$ spiking activity in islet shows on-off intermittency with scaling of spiking amplitudes, and stimulus dependent autoassociative memory features. We use a simple spin glass-like model for the functional network of a $\beta$-cell collective to describe these findings and argue that Ca$^{2+}$ spike trains produced by collective sensing of $\beta$-cells constitute part of the islet metabolic code that regulates insulin release and limits the islet size.