Fig. 3: Differences in PDX1 and MAFA levels contribute to islet signaling.

a–c Ca²⁺ fluxes (a) in response to glucose (b) or glucose + KCl (c) are impaired in B-MAT islets, also shown by representative images (d) (n = 34 islets/4 animals; unpaired t-test) (scale bar = 40 µm). Inset in (a) shows an inverse correlation between glucose-stimulated Ca²⁺ amplitude and BFP expression in individual β-cells (Pdx1-BFP; n = 6 islets/3 animals; R² = 0.21, P < 0.0001) (G11, 11 mM glucose; KCl, 10 mM). e No diffeences in the % glucose-responsive β-cells are detected in B-MAT islets (n = 34 islets/4 animals; unpaired t-test). f–h As for (a–c), but using Fura2 (n = 33 islets/4 animals; unpaired t-test). i Expression of genes encoding CACNA1D and CACNB2 Ca²⁺ channel subunits is reduced in B-MAT islets (n = 8 animals; paired t-test). j, k Ca²⁺ pulse duration is reduced in B-MAT islets, as shown by summary bar graph (j) and traces (k) (n = 8 islets/4 animals; unpaired t-test). l, m ATP/ADP ratios are reduced in B-MAT islets, as shown by mean traces (l) and summary bar graph (m) (n = 40 islets/4 animals; unpaired t-test). n, o GCK expression (n) tends to be reduced in B-MAT islets (n = 10 islets/2 animals; paired t-test), although Gck levels are normal (o) (n = 7 animals; paired t-test) (scale bar = 15 µm). p, q Ca²⁺ (p) and ATP/ADP (q) responses to increasing glucose concentration are decreased in B-MAT islets (Ca²⁺: n = 11 islets/5 animals; two-way ANOVA F = 20.36, DF = 4) (ATP/ADP: n = 37 islets/5 animals, two-way ANOVA; F = 6.10, DF = 4) (Bonferroni’s multiple comparison). r, s Mean traces (r) and bar graph (s) showing reduced cAMP levels in response to glucose and forskolin (FSK, 100 μM) in B-MAT islets (n = 13 islets; unpaired t-test). t Adcy8 expression remains unchanged in B-MAT islets (n = 6 animals; paired t-test). u G6pc2 and Ascl1 are up- and down-regulated, respectively, in B-MAT islets (n = 6 animals; paired t-test). Color scale shows Ca²⁺ as min (0%) to max (100%) value. Bar graphs and traces show the mean ± SEM. All tests are two-sided where relevant. CTCF-corrected total cell fluorescence.