INS and type 2 diabetes mellitus: In situ proinsulin and insulin imaging quantification analysis (Fig. 2b,e; ESM Fig. 4) showed that proinsulin area progressively increased from NGT to type 2 diabetes (p<0.0001) (NGT=0.054; IGT=0.085; type 2 diabetes=0.117 [proinsulin area/islet area mean values]) (Fig. 2c; ESM Figs 3, 4), while insulin area did not significantly differ among the three groups (Fig. 2d; ESM Figs 3, 4).