Pancreatic plasticity — mechanisms and pathways of beta cell fate change in health, regeneration and disease

The adult pancreas possesses limited capacity for regeneration. Evidence suggests conversion between terminally differentiated pancreatic cells, either through transdifferentiation or dedifferentiation, but the extent, cellular origins and physiological relevance of these processes are not fully understood. Key insights have emerged from studies of pancreatic injury and stress, which induce cellular reprogramming and expansion of the beta cell compartment. Additionally, model organisms such as zebrafish and axolotls exhibit a greater capacity for pancreatic regeneration, providing evolutionary perspectives. Understanding these mechanisms may enable manipulation of endogenous regenerative responses for translational applications. In this review, we summarise recent studies on pancreatic plasticity and the mechanisms underlying beta cell regeneration and discuss how these insights may guide new regenerative strategies for the treatment of diabetes.