Pancreatic β cell regeneration: To β or not to β

Diabetes is a major worldwide health problem which results from the loss and/or dysfunction of pancreatic insulin-producing β cells in the pancreas. Therefore, there is great interest in understanding the endogenous capacity of β cells to regenerate under normal or pathological conditions, with the goal of restoring functional β cell mass in patients with diabetes. Here, we summarize the current status of β cell regeneration research, which has been broadly divided into three in vivo mechanisms: 1. proliferation of existing β cells; 2. neogenesis of β cells from adult ductal progenitors; and 3. transdifferentiation of other cell types into β cells. We discuss the evidence and controversies for each mechanism in mice and humans, as well as the prospect of using these approaches for the treatment of diabetes.