Using db/db mice as a model of obesity-induced T2D along with background-matched BKS controls, we observed a β-cell-specific increase in H2AX (both punctate and pan-nuclear) in 8-week-old db/db mice, a stage marked by hyperglycemia preceding diabetes onset (Fig. 5A–C, Supplementary Fig. 5A). This evidence concerns the gene H2AX and obesity due to melanocortin 4 receptor deficiency.