Abstract
β-cell number and/or function is reduced in diabetes. Thus, inducing the formation of new β-cells has been a major goal of diabetes research. However, the pathway(s) by which new β-cells form when preexisting β-cells are decreased in number or cease to function has remained obscure. Many pathways have been proposed, but definitive evidence, particularly in humans, has been lacking. Replication of preexisting β-cells, neogenesis from ducts, redifferentiation from β-cells that dedifferentiated under metabolic stress, and transdifferentiation from other cell types, particularly within the islet, are the major mechanisms that have been proposed for generating increased numbers of functional β-cells. Here, I will discuss those approaches critically, with particular attention to transdifferentiation of preexisting α-cells to β-cells.