Mosaic ablation of pancreatic β-cells induces de-differentiation and repetitive proliferation of residual β-cells in adult mice

Diabetes mellitus is induced by quantitative and qualitative decline in pancreatic β cells. Although its radical therapy has not yet been established, β cell regeneration is a promising option. We investigate here two mouse models of β cell regeneration induced after ∼80% reduction in β cell number: Cre/loxP-mediated β cell ablation and partial pancreatectomy. Cre/loxP-mediated, mosaic-pattern of β cell ablation by diphtheria toxin (DT) prompted rapid β cell replenishment through repeated proliferation of rare, highly proliferative DT receptor-negative β cells along with increase in