This study investigates the ability of adult pancreatic α-cells to regenerate into β-cells after extreme β-cell loss, a condition similar to Type 1 diabetes (T1D). Using a transgenic model of diphtheria toxin (DT)-induced acute selective near-total β-cell ablation, the researchers found that mice could survive and exhibit β-cell mass augmentation over time when given insulin. Lineage-tracing experiments revealed that a significant fraction of the regenerated β-cells derived from α-cells, indicating a previously unrecognized degree of pancreatic cell plasticity. The findings suggest that inter-endocrine spontaneous adult cell conversion could be harnessed for producing β-cells for diabetes therapies, either through differentiation in vitro or induced regeneration. The study highlights the potential of α-cells as a source of β-cell regeneration and the importance of understanding cell plasticity in regenerative medicine.This study investigates the ability of adult pancreatic α-cells to regenerate into β-cells after extreme β-cell loss, a condition similar to Type 1 diabetes (T1D). Using a transgenic model of diphtheria toxin (DT)-induced acute selective near-total β-cell ablation, the researchers found that mice could survive and exhibit β-cell mass augmentation over time when given insulin. Lineage-tracing experiments revealed that a significant fraction of the regenerated β-cells derived from α-cells, indicating a previously unrecognized degree of pancreatic cell plasticity. The findings suggest that inter-endocrine spontaneous adult cell conversion could be harnessed for producing β-cells for diabetes therapies, either through differentiation in vitro or induced regeneration. The study highlights the potential of α-cells as a source of β-cell regeneration and the importance of understanding cell plasticity in regenerative medicine.