How to make a functional β-cell

Insulin-secreting pancreatic beta-cells are essential regulators of mammalian metabolism. The absence of functional beta-cells leads to hyperglycemia and diabetes, making patients dependent on exogenously supplied insulin. Recent insights into beta-cell development, combined with the discovery of pluripotent stem cells, have led to an unprecedented opportunity to generate new beta-cells for transplantation therapy and drug screening. Progress has also been made in converting terminally differentiated cell types into beta-cells using transcriptional regulators identified as key players in normal development, and in identifying conditions that induce beta-cell replication in vivo and in vitro. Here, we summarize what is currently known about how these strategies could be utilized to generate new beta-cells and highlight how further study into the mechanisms governing later stages of differentiation and the acquisition of functional capabilities could inform this effort.