In the pancreas, insulin-producing β-cells are long-lived and generally replicate seldom. They can do so, however, after increased metabolic demand or after injury. Here, a new transgenic model is developed in which β-cells are nearly completely ablated in mice. If given insulin, these mice survive, and grow new β-cells. Lineage-tracing shows that these new β-cells come from α-cells, revealing a previously disregarded degree of pancreatic cell plasticity.