Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.28.358457v1?rss=1 Authors: Dwulet, J. M., Briggs, J. K., Benninger, R. K. Abstract: The islets of Langerhans exist as a multicellular network that is important for the regulation of blood glucose levels. The majority of cells in the islet are insulin-producing {beta}-cells, which are excitable cells that are electrically coupled via gap junction channels. {beta}-cells have long been known to display heterogeneous functionality. However, due to gap junction electrical coupling, {beta}-cells show coordinated [Ca2+] oscillations when stimulated with glucose, and global quiescence when unstimulated. Small subpopulations of highly functional {beta}-cells have been suggested to control the dynamics of [Ca2+] and insulin release across the islet. In this study, we investigated the theoretical basis of whether small subpopulations of {beta}-cells can disproportionality control islet [Ca2+] dynamics. Using a multicellular model of the islet, we generated continuous or bimodal distributions of {beta}-cell heterogeneity and examined how islet [Ca2+] dynamics depended on the presence of cells with increased excitability or increased oscillation frequency. We found that the islet was susceptible to marked suppression of [Ca2+] when a ~10% population of cells with high metabolic activity was hyperpolarized; where hyperpolarizing cells with normal metabolic activity had little effect. However, when these highly metabolic cells were removed from the islet model, near normal [Ca2+] remained. Similarly, when ~10% of cells with either the highest frequency or earliest elevations in [Ca2+] were removed from the islet, the [Ca2+] oscillation frequency remained largely unchanged. Overall these results indicate that small populations of {beta}-cells with either increased excitability or increased frequency, or signatures of [Ca2+] dynamics that suggest such properties, are unable to disproportionately control islet-wide [Ca2+] via gap junction coupling. As such, we need to reconsider the physiological basis for such small {beta}-cell populations or the mechanism by which they may be acting to control normal islet function. Copy rights belong to original authors. Visit the link for more info