@article {Podobnik765933, author = {Boris Podobnik and Dean Koro{\v s}ak and Ma{\v s}a Skelin Klemen and Andra{\v z} Sto{\v z}er and Jurij Dolen{\v s}ek and Marjan Slak Rupnik and Plamen Ch. Ivanov and Petter Holme and Marko Jusup}, title = {β-cells operate collectively to help maintain glucose homeostasis}, elocation-id = {765933}, year = {2019}, doi = {10.1101/765933}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Residing in the islets of Langerhans in the pancreas, beta cells contribute to glucose homeostasis by managing the body{\textquoteright}s insulin supply. A circulating hypothesis has been that healthy beta cells heavily engage in cell-to-cell communication to perform their homeostatic function. We provide strong evidence in favor of this hypothesis in the form of (i) a dynamical network model that faithfully mimics fast calcium oscillations in response to above-threshold glucose stimulation and (ii) 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 beta-cell activity thanks to increasing coordination through gap-junctional signaling and paracrine interactions. The model further suggests how the conservation of entire cell-cell conductance, observed in coupled but not uncoupled beta cells, emerges as a collective phenomenon. An overall implication is that improving the ability to monitor beta-cell signaling should offer means to better understand the pathogenesis of diabetes mellitus.}, URL = {https://www.biorxiv.org/content/early/2019/09/12/765933}, eprint = {https://www.biorxiv.org/content/early/2019/09/12/765933.full.pdf}, journal = {bioRxiv} }