Fig. 9: Maintaining PDX1^LOW:PDX1^HIGH β-cell balance protects against islet failure.

a–c A significant decrease in the proportion of PDX1^HIGH β-cells is detected in palmitate-treated islets (a), and this can be reversed using Ad-M3C (b), as shown by representative images (c) (n = 7 islets/4 animals; two-way ANOVA, Bonferroni’s multiple comparison) (Palm: F = 4.28, DF = 20) (Palm + Ad-M3C: F = 0.90, DF = 20) (BSA, bovine serum albumin; Palm, 0.5 mM palmitate for 48 h) (scale bar = 42.5 µm). Note that the same BSA-only (control) PDX1 fluorescence intensity distribution is shown in both graphs (a) and (b) to allow cross-comparison (the experiments were performed in parallel). d–f Ca²⁺ responses to glucose (d) and KCl (e) are blunted in palmitate-treated, but not palmitate + Ad-M3C-treated islets (n = 27 islets/4 animals; one-way ANOVA, Sidak’s multiple comparison) (G11: F = 18.80, DF = 2) (KCl: F = 23.13, DF = 2), as shown by mean traces (f). g Schematic showing that a decrease in the proportion of PDX1^LOW/MAFA^LOW β-cells leads to altered islet Ca²⁺ fluxes, decreased expression of Ca²⁺-dependent genes such as Ascl1, and broader changes to β-cell function, including impaired ATP/ADP and insulin responses to glucose. Bar graphs and traces show the mean ± SEM. Box-and-whiskers plot shows median and min-max. All tests are two-sided where relevant.