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bioRxiv · 10.1101/765933

β-cells operate collectively to help maintain glucose homeostasis

Podobnik, B.·Korosak, D.·Skelin Klemen, M.·Stozer, A.·Dolensek, J.·Slak Rupnik, M.·Ivanov, P. C.·Holme, P.·Jusup, M.
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Abstract

Residing in the islets of Langerhans in the pancreas, beta cells contribute to glucose homeostasis by managing the bodys 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.

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Podobnik, B., Korosak, D., Skelin Klemen, M., Stozer, A., Dolensek, J., Slak Rupnik, M., Ivanov, P. C., Holme, P., Jusup, M.. 2019-09-12. β-cells operate collectively to help maintain glucose homeostasis. https://doi.org/10.1101/765933

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