Collective Sensing of β-Cells Generates the Metabolic Code

• Main Authors: Dean Korošak, Marjan Slak Rupnik
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2018-01-01
• Series: Frontiers in Physiology
• Subjects: collective sensing; pancreatic islets; spin glass models; metabolic code; Ca2+ imaging; Ca2+ signaling
• Online Access: http://journal.frontiersin.org/article/10.3389/fphys.2018.00031/full

Major part of a pancreatic islet is composed of β-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. β-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, β-cells collectively respond with expression of a series of transient Ca2+ changes on several temporal scales. Here we reanalyze a set of Ca2+ 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 Ca2+ 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 β-cell collective to describe these findings and argue that Ca2+ spike trains produced by collective sensing of β-cells constitute part of the islet metabolic code that regulates insulin release and limits the islet size.