| First Author | Talchai C | Year | 2012 |
| Journal | Nat Genet | Volume | 44 |
| Issue | 4 | Pages | 406-12, S1 |
| PubMed ID | 22406641 | Mgi Jnum | J:183890 |
| Mgi Id | MGI:5319468 | Doi | 10.1038/ng.2215 |
| Citation | Talchai C, et al. (2012) Generation of functional insulin-producing cells in the gut by Foxo1 ablation. Nat Genet 44(4):406-12, S1 |
| abstractText | Restoration of regulated insulin secretion is the ultimate goal of therapy for type 1 diabetes. Here, we show that, unexpectedly, somatic ablation of Foxo1 in Neurog3(+) enteroendocrine progenitor cells gives rise to gut insulin-positive (Ins(+)) cells that express markers of mature beta cells and secrete bioactive insulin as well as C-peptide in response to glucose and sulfonylureas. Lineage tracing experiments showed that gut Ins(+) cells arise cell autonomously from Foxo1-deficient cells. Inducible Foxo1 ablation in adult mice also resulted in the generation of gut Ins(+) cells. Following ablation by the beta-cell toxin streptozotocin, gut Ins(+) cells regenerate and produce insulin, reversing hyperglycemia in mice. The data indicate that Neurog3(+) enteroendocrine progenitors require active Foxo1 to prevent differentiation into Ins(+) cells. Foxo1 ablation in gut epithelium may provide an approach to restore insulin production in type 1 diabetes. |
