title: How to make a functional β-cell.
abstract: Insulin-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.
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Felicia W
authors.initials: FW
authors.lastname: Pagliuca
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Melton
mesh_terms: D061354:Acinar Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D065150:Cellular Reprogramming; D003920:Diabetes Mellitus / Q000473:pathology / Q000628:therapy*; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000166:cytology / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D005947:Glucose
keywords: Diabetes mellitus; Mammalian metabolism; β cell