| First Author | Courtney M | Year | 2013 |
| Journal | PLoS Genet | Volume | 9 |
| Issue | 10 | Pages | e1003934 |
| PubMed ID | 24204325 | Mgi Jnum | J:205133 |
| Mgi Id | MGI:5544141 | Doi | 10.1371/journal.pgen.1003934 |
| Citation | Courtney M, et al. (2013) The inactivation of Arx in pancreatic alpha-cells triggers their neogenesis and conversion into functional beta-like cells. PLoS Genet 9(10):e1003934 |
| abstractText | Recently, it was demonstrated that pancreatic new-born glucagon-producing cells can regenerate and convert into insulin-producing beta-like cells through the ectopic expression of a single gene, Pax4. Here, combining conditional loss-of-function and lineage tracing approaches, we show that the selective inhibition of the Arx gene in alpha-cells is sufficient to promote the conversion of adult alpha-cells into beta-like cells at any age. Interestingly, this conversion induces the continuous mobilization of duct-lining precursor cells to adopt an endocrine cell fate, the glucagon(+) cells thereby generated being subsequently converted into beta-like cells upon Arx inhibition. Of interest, through the generation and analysis of Arx and Pax4 conditional double-mutants, we provide evidence that Pax4 is dispensable for these regeneration processes, indicating that Arx represents the main trigger of alpha-cell-mediated beta-like cell neogenesis. Importantly, the loss of Arx in alpha-cells is sufficient to regenerate a functional beta-cell mass and thereby reverse diabetes following toxin-induced beta-cell depletion. Our data therefore suggest that strategies aiming at inhibiting the expression of Arx, or its molecular targets/co-factors, may pave new avenues for the treatment of diabetes. |
