Pagliuca, FeliciaMelton, Douglas2017-06-092013Pagliuca, F. W., and D. A. Melton. 2013. “How to Make a Functional β-Cell.” Development 140 (12) (June 15): 2472–2483. doi:10.1242/dev.093187.0950-1991http://nrs.harvard.edu/urn-3:HUL.InstRepos:32969834Insulin-secreting pancreatic β-cells are essential regulators of mammalian metabolism. The absence of functional β-cells leads to hyperglycemia and diabetes, making patients dependent on exogenously supplied insulin. Recent insights into β-cell development, combined with the discovery of pluripotent stem cells, have led to an unprecedented opportunity to generate new β-cells for transplantation therapy and drug screening. Progress has also been made in converting terminally differentiated cell types into β-cells using transcriptional regulators identified as key players in normal development, and in identifying conditions that induce β-cell replication in vivo and in vitro. Here, we summarize what is currently known about how these strategies could be utilized to generate new β-cells and highlight how further study into the mechanisms governing later stages of differentiation and the acquisition of functional capabilities could inform this effort.en-USJournal Article2014-02-07Pagliuca, FW, Melton DA2017-06-0910.1242/dev.093187