Slow and steady is the key to β‐cell replication

•  Diabetes is a chronic disease of failed glucose homeostasis •  Structure and function of the adult pancreas •  Diabetes is an attractive target for cellular replacement therapy •  In vitro differentiation of β‐cells from embryonic stem cells •  β‐cell maintenance and expansion •  Strong evidence that new β‐cells come from old β‐cells •  All β‐cells contribute equally to islet growth and maintenance •  Putative pancreatic stem cells •  Reported evidence for bone marrow stem cells giving rise to β‐cells •  Reported evidence for spleen stem cells giving rise to β‐cells •  Reported evidence for ductal stem cells giving rise to β‐cells •  Reported evidence for acini stem cells giving rise to β‐cells •  Reported evidence for islet and/or pancreatic stem cells giving rise to β‐cells •  β‐cell turnover •  β‐cell mass is dynamic •  β‐cell replication changes with age •  β‐cell replication increases during pregnancy •  β‐cell replication increases in cases of increased blood glucose and/or insulin resistance •  β‐cell replication is regulated by cell cycle genes •  The elusive circulating β‐cell growth factor •  Increasing β‐cell replication in vivo•  In vitro culture of β‐cells •  SummaryAbstract The β‐cells of the pancreas are responsible for insulin production and their destruction results in type I diabetes. β‐cell maintenance, growth and regenerative repair is thought to occur predominately, if not exclusively, through the replication of existing β‐cells, not via an adult stem cell. It was recently found that all β‐cells contribute equally to islet growth and maintenance. The fact that all β‐cells replicate homogeneously makes it possible to set up straightforward screens for factors that increase β‐cell replication either In vitro or in vivo . It is possible that a circulating factor may be capable of increasing β‐cell replication or that intrinsic cell cycle regulators may affect β‐cell growth. An improved understanding of the in vivo maintenance and growth of β‐cells will facilitate efforts to expand β‐cells In vitro and may lead to new treatments for diabetes.