Figure 1.

Inhibition of hub cells can abolish whole-islet Ca²⁺ activity. (A) ${\left[C{a}^{2+}\right]}_i$ activity of mouse islet model when the GJ conductance for non-hubs $\left(\left[G_{non-hub}\right]\right)$ is sampled from a uniform distribution over the interval 6.5-7.5mM $(\left[G_{non-hub}\right]\sim U\left(6.5,7.5\right)$). The model produces robust ${\left[C{a}^{2+}\right]}_i$ oscillations in response to high glucose. (B) ${\left[C{a}^{2+}\right]}_i$ activity of mouse islet model when the GJ conductance for non-hubs $\left(\left[G_{non-hub}\right]\right)$ is sampled from a uniform distribution over the interval 6.0-7.0mM $\left(\left[G_{non-hub}\right]\sim U\left(6,7\right)\right).$ The model produces robust ${\left[C{a}^{2+}\right]}_i$ oscillations in response to high glucose. Simulated islet (C) ${\left[C{a}^{2+}\right]}_i$activity during inhibition of hub cells. The number of hub cells inhibited is represented as the % of all cells in the islet (750 cells). The different simulations are for sampling $\left[G_{non-hub}\right]$ from different uniform distributions. Note how hub inhibition has the strongest effect when $\left[G_{non-hub}\right]\sim U\left(6,7\right)$. Simulated islet (D) ${\left[C{a}^{2+}\right]}_i$ activity during inhibition of hub or non-hub cells. When $\left[G_{non-hub}\right]\sim U\left(6,7\right)$ mM, hub inhibition strongly suppresses whole-islet ${\left[C{a}^{2+}\right]}_i$. In contrast, when $\left[G_{non-hub}\right]\sim U\left(6.5,7.5\right)$ mM, hub inhibition has little effect on whole-islet ${\left[C{a}^{2+}\right]}_i$. Mean (E) ${\left[C{a}^{2+}\right]}_i$ for all β-cells in a mouse islet model, during high glucose condition. Raster plot showing ${\left[C{a}^{2+}\right]}_i$ activity in each β-cell. 3D plot of ${\left[C{a}^{2+}\right]}_i$ for each β-cell in the islet model at time points (1) and (2). Mean (F) ${\left[C{a}^{2+}\right]}_i$ for all β-cells in a mouse islet model, during hub inhibition and non-hub inhibition. 45 hub cells or non-hub cells where inhibited simultaneously. Raster plot showing ${\left[C{a}^{2+}\right]}_i$ activity in each β-cell during the hub inhibition condition. 3D plot of ${\left[C{a}^{2+}\right]}_i$ for each β-cell in the islet model at time points (1) and (2) during hub inhibition. Mean (G) ${\left[C{a}^{2+}\right]}_i$ for all β-cells in a mouse islet model, during recovery from hub inhibition. Raster plot showing ${\left[C{a}^{2+}\right]}_i$ activity in each β-cell. 3D plot of ${\left[C{a}^{2+}\right]}_i$ for each β-cell in the islet model at time points (1) and (2). cf. S1 Video.