Figure 1. β Cell exocytosis is impaired in T2D.

(A) Compared with islets of donors with no diabetes (ND; n = 63), glucose-stimulated insulin secretion is impaired from islets of donors with type 2 diabetes (T2D; n = 17). (B) In both sets of donors (average 6.7 years’ duration of T2D) islet insulin content is not different. (C and D) Cumulative distribution of exocytotic responses of β cells from the same donors, measured by patch-clamp electrophysiology. Glucose (10 mM; red) amplifies the (C) exocytotic responses of ND β cells (n = 701 cells) (D) but not T2D β cells (n = 156 cells). (E) Impaired glucose-stimulated insulin secretion observed in the subgroup of ND (n = 17 donors) and T2D (n = 7 donors) subsequently used for TIRF imaging. (F) In individual β cells expressing NPY-EGFP, fusion events (red circles) observed by live-cell TIRF microscopy at 5 mM glucose in ND β cells, a heatmap of fusion event density, and Voronoi diagram used to separate exocytosis sites (scale bar: 5 μm). (G) Representative recordings from the areas indicated in F. (H) The nonrandom nature of fusion events in ND β cells is demonstrated by spatial K-function calculation (red line) greater than the simulated (dashed lines) maximum. (I–K) The same as F–H but in a T2D β cell, where events appear more randomly distributed (scale bar: 5 μm). Significance was determined by (B) Mann-Whitney test or (A and E) Kruskal-Wallis 1-way ANOVA followed by Mann-Whitney posttest. *P < 0.05; ***P < 0.001.