INS and diabetes mellitus: This increase was accompanied by a fractional decrease of insulin-positive cells (Figure 3E, quantified in Figure 3G) and a higher fraction of β cells that exhibited weaker insulin immunostaining, consistent with a decrease of islet insulin (Figure 2D and Supplemental Figure 1B) and an increase in islet cell heterogeneity suggested to be linked to diabetes in humans and several rodent models (18, 28–33).