| First Author | Rachdi L | Year | 2006 |
| Journal | Diabetes | Volume | 55 |
| Issue | 12 | Pages | 3520-8 |
| PubMed ID | 17130500 | Mgi Jnum | J:120997 |
| Mgi Id | MGI:3709096 | Doi | 10.2337/db06-0861 |
| Citation | Rachdi L, et al. (2006) Differential effects of p27 in regulation of beta-cell mass during development, neonatal period, and adult life. Diabetes 55(12):3520-8 |
| abstractText | beta-Cell cycle progression and proliferation are critical to maintain beta-cell mass in adult mice. Of the cell cycle inhibitors, p27Kip1 is thought to be the primary modulator of the proliferative status in most cell types. p27 plays a role in beta-cell adaptation in genetic models of insulin resistance. To study the role of p27 in beta-cells during physiological conditions and at different stages of beta-cell differentiation, we studied mice deficient of or overexpressing p27. Experiments in p27-deficient mice showed improved glucose tolerance and hyperinsulinemia. These changes were associated with increased islet mass and proliferation. The experiments overexpressing p27 in beta-cells were performed using a doxycycline-inducible model. Interestingly, overexpression of p27 for 16 weeks in beta-cells from adult mice had no effect on glucose tolerance, beta-cell mass, or proliferation. In contrast, induction of p27 expression during beta-cell development or early neonatal period resulted in severe glucose intolerance and reduced beta-cell mass by decreased proliferation. These changes were reversible upon discontinuation of doxycycline. These experiments suggest that p27 is a critical molecule for beta-cell proliferation during beta-cell development and early postnatal life but not for maintenance of adult mass. |
