Diabetes results from the absolute or relative deficiency of insulin-producing beta cells. The prospect that non-beta pancreatic cells could be harnessed to become beta cells has led to interest in understanding the plasticity of pancreatic cells. Recent studies, however, have shown that adult beta cells are largely derived from preexisting beta cells. In this issue of the JCI, Desai et al. show that acinar cells, the major cell type in the pancreas, do not contribute to new beta cells formed during pancreatic regeneration (see the related article beginning on page 971). These studies suggest that the fate of adult pancreatic cell lineages is immutable. However, also in this issue of the JCI, Collombat et al. demonstrate that inducing a single transcription factor named Arx in adult beta cells causes these cells to undergo massive transdifferentiation into alpha and pancreatic polypeptide endocrine cells (see the related article beginning on page 961). This finding points to an unexpected plasticity of postnatal pancreatic endocrine cells.