Increased transdifferentiation of alpha to beta cells in FSTL3 knockout mice

Fairbanks scientists collaborated with UMass-Amherst faculty to determine whether the increase in insulin-producing beta cells observed numerous times in FSTL3 knockout mice results, at least in part, from enhancing alpha to beta cell transdifferentiation. A process called “lineage tracing” in which alpha cells are permanently marked with a yellow tag was used to monitor their fate over time. Alpha cells typically produce glucagon, a hormone that counteracts insulin and helps prevent glucose from falling too much. Yellow cells that now produce insulin (a hallmark of beta cells) were identified in wild type mice and the number of these cells was increased significantly in mice in which the FSTL3 gene was inactivated (FSTL3 Knockout mice) that have elevated activin signaling.

These results support our hypothesis that activin and related growth factors enhance alpha to beta cell transdifferentiation resulting in increased numbers of functional beta cells.

These results were published in the journal Endocrinology in March 2016 (Endocrinology 157: 1043–1054, 2016). View in Pubmed