Simulations predicting how cells from a bimodal distribution characterized by early phase cells contribute to islet frequency.
A). Schematic of frequency across simulated islet with a bimodal distribution in GK activity. B). Schematic of phase lag across simulated islet with a bimodal distribution in GK activity. C). Representative time courses of [Ca2+] for 6 cells in simulated islet in A (and B) in a simulation with full (120pS) coupling conductance. Blue traces are high frequency cells, red traces are low frequency cells. Inset: Close up of rise of [Ca2+] oscillation showing phase lags. D). Phase lag from islet average of top 1% or 10% of early phase, late phase cells, or random cells. E). Average intrinsic oscillation frequencies of all cells and 1% or 10% of early phase cells, or 1% or 10% of late phase cells when re-simulated in the absence of gap junction coupling (0pS). F). Average kglc from all cells and top 1% or 10% of early phase cells or late phase cells across simulated islet (normalized to average kglc). G). Change in frequency of islet with indicated populations removed with respect to control islet with all cells present. H). Change in frequency when early phase cells are removed compared to average oscillation frequency of remaining cells that indicates the expected oscillation frequency. I). Same as H. but for simulations where late phase cells are removed. Repeated measures one-way ANOVA with Tukey post-hoc analysis was performed for simulations in D-G and a Student’s paired t-test was performed for H and I to test for significance. Error bars are mean ± s.e.m. Significance values: ns indicates not significant (p>.05), * indicates significant difference (p < .05), ** indicates significant difference (p < .01), *** indicates significant difference (p < .001), **** indicates significant difference (p < .0001). Data representative of 5 simulations with differing random number seeds. Random removal of cells across the islet was used where random cells removed is indicated.