Functional beta-cell maturation is marked by an increased glucose threshold and by expression of urocortin 3

Cultured human pluripotent stem cells can be differentiated to immature pancreatic beta cells, but no one has yet succeeded in maturing these cells in vitro. Blum et al. define markers of beta-cell maturation that can be used to screen conditions for generating fully functional beta cells. Insulin-expressing cells that have been differentiated from human pluripotent stem cells in vitro lack the glucose responsiveness characteristic of mature beta cells. Beta-cell maturation in mice was studied to find genetic markers that enable screens for factors that induce bona fide beta cells in vitro. We find that functional beta-cell maturation is marked by an increase in the glucose threshold for insulin secretion and by expression of the gene urocortin 3.