| First Author | Blum B | Year | 2014 |
| Journal | Elife | Volume | 3 |
| Pages | e02809 | PubMed ID | 25233132 |
| Mgi Jnum | J:218054 | Mgi Id | MGI:5616492 |
| Doi | 10.7554/eLife.02809 | Citation | Blum B, et al. (2014) Reversal of beta cell de-differentiation by a small molecule inhibitor of the TGFbeta pathway. Elife 3:e02809 |
| abstractText | Dysfunction or death of pancreatic beta cells underlies both types of diabetes. This functional decline begins with beta cell stress and de-differentiation. Current drugs for type 2 diabetes (T2D) lower blood glucose levels but they do not directly alleviate beta cell stress nor prevent, let alone reverse, beta cell de-differentiation. We show here that Urocortin 3 (Ucn3), a marker for mature beta cells, is down-regulated in the early stages of T2D in mice and when beta cells are stressed in vitro. Using an insulin expression-coupled lineage tracer, with Ucn3 as a reporter for the mature beta cell state, we screen for factors that reverse beta cell de-differentiation. We find that a small molecule inhibitor of TGFbeta receptor I (Alk5) protects cells from the loss of key beta cell transcription factors and restores a mature beta cell identity even after exposure to prolonged and severe diabetes. |
