| First Author | Cai EP | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 36 | Pages | 14723-8 |
| PubMed ID | 23946427 | Mgi Jnum | J:200985 |
| Mgi Id | MGI:5510610 | Doi | 10.1073/pnas.1303386110 |
| Citation | Cai EP, et al. (2013) Retinoblastoma tumor suppressor protein in pancreatic progenitors controls alpha- and beta-cell fate. Proc Natl Acad Sci U S A 110(36):14723-8 |
| abstractText | Pancreatic endocrine cells expand rapidly during embryogenesis by neogenesis and proliferation, but during adulthood, islet cells have a very slow turnover. Disruption of murine retinoblastoma tumor suppressor protein (Rb) in mature pancreatic beta-cells has a limited effect on cell proliferation. Here we show that deletion of Rb during embryogenesis in islet progenitors leads to an increase in the neurogenin 3-expressing precursor cell population, which persists in the postnatal period and is associated with increased beta-cell mass in adults. In contrast, Rb-deficient islet precursors, through repression of the cell fate factor aristaless related homeobox, result in decreased alpha-cell mass. The opposing effect on survival of Rb-deficient alpha- and beta-cells was a result of opposing effects on p53 in these cell types. As a consequence, loss of Rb in islet precursors led to a reduced alpha- to beta-cell ratio, leading to improved glucose homeostasis and protection against diabetes. |
