We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Differential effects of p27 in regulation of beta-cell mass during development, neonatal period, and adult life.
- Authors
Rachdi L; Balcazar N; Elghazi L; Barker DJ; Krits I; Kiyokawa H; Bernal-Mizrachi E; Rachdi, Latif; Balcazar, Norman; Elghazi, Lynda; Barker, Daniel J; Krits, Irina; Kiyokawa, Hiroaki; Bernal-Mizrachi, Ernesto
- Abstract
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.
- Publication
Diabetes, 2006, Vol 55, Issue 12, p3520
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db06-0861