| First Author | Brown ML | Year | 2016 |
| Journal | Endocrinology | Volume | 157 |
| Issue | 3 | Pages | 1043-54 |
| PubMed ID | 26727106 | Mgi Jnum | J:233840 |
| Mgi Id | MGI:5788208 | Doi | 10.1210/en.2015-1793 |
| Citation | Brown ML, et al. (2016) Activin Enhances alpha- to beta-Cell Transdifferentiation as a Source For beta-Cells In Male FSTL3 Knockout Mice. Endocrinology 157(3):1043-54 |
| abstractText | Diabetes results from inadequate beta-cell number and/or function to control serum glucose concentrations so that replacement of lost beta-cells could become a viable therapy for diabetes. In addition to embryonic stem cell sources for new beta-cells, evidence for transdifferentiation/reprogramming of non-beta-cells to functional beta-cells is accumulating. In addition, de-differentiation of beta-cells observed in diabetes and their subsequent conversion to alpha-cells raises the possibility that adult islet cell fate is malleable and controlled by local hormonal and/or environmental cues. We previously demonstrated that inactivation of the activin antagonist, follistatin-like 3 (FSTL3) resulted in beta-cell expansion and improved glucose homeostasis in the absence of beta-cell proliferation. We recently reported that activin directly suppressed expression of critical alpha-cell genes while increasing expression of beta-cell genes, supporting the hypothesis that activin is one of the local hormones controlling islet cell fate and that increased activin signaling accelerates alpha- to beta-cell transdifferentiation. We tested this hypothesis using Gluc-Cre/yellow fluorescent protein (YFP) alpha-cell lineage tracing technology combined with FSTL3 knockout (KO) mice to label alpha-cells with YFP. Flow cytometry was used to quantify unlabeled and labeled alpha- and beta-cells. We found that Ins+/YFP+ cells were significantly increased in FSTL3 KO mice compared with wild type littermates. Labeled Ins+/YFP+ cells increased significantly with age in FSTL3 KO mice but not wild type littermates. Sorting results were substantiated by counting fluorescently labeled cells in pancreatic sections. Activin treatment of isolated islets significantly increased the number of YFP+/Ins+ cells. These results suggest that alpha- to beta-cell transdifferentiation is influenced by activin signaling and may contribute substantially to beta-cell mass. |
