Researchers have discovered new markers that allow them to distinguish between mature β cells that produce insulin in a regulated fashion and immature β cells that do not. A major goal of diabetes research is to turn stem and/or progenitor cells in the laboratory into insulin-producing β cells that can be transplanted into people. Importantly, those cells must release insulin properly in response to glucose to be a viable therapeutic option. Significant progress has been made in generating immature β cells in the lab, but these cells do not respond appropriately to glucose. In order to develop strategies to turn immature β cells into mature cells, it would be useful if scientists had experimental markers that helped them distinguish between the two cell types. The authors discovered that immature cells isolated from newborn mice released insulin in response to lower glucose levels than mature cells isolated from adult mice. In other words, the immature cells had a lower “glucose threshold” for releasing insulin. The researchers then compared how the levels of various proteins differed between the two groups of cells. They found that a protein called urocortin 3 was present at much higher levels in functionally mature β cells than in immature cells in both mice and humans. These discoveries provide important new tools to scientists testing experimental strategies to generate mature β cells in the lab—they could use differences in glucose threshold and urocortin 3 levels as markers of β cell maturation. These findings can facilitate research to turn stem and/or progenitor cells into mature β cells as a possible therapy for people with diabetes.
Blum B, Hrvatin SS, Schuetz C, Bonal C, Rezania A, and Melton DA. Functional beta-cell maturation is marked by an increased glucose threshold and by expression of urocortin 3. Nat Biotechnol 30: 261-264, 2012.