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- Title
Differential Effects of p27 in Regulation of β-Cell Mass During Development, Neonatal Period, and Adult Life.
- Authors
Rachdi, Latif; Balcazar, Norman; Elghazi, Lynda; Barker, Daniel J.; Krits, Irina; Kiyokawa, Hiroaki; Bernal-Mizrachi, Ernesto
- Abstract
β-Cell cycle progression and proliferation are critical to maintain β-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 β-cell adaptation in genetic models of insulin resistance. To study the role of p27 in β-cells during physiological conditions and at different stages of β-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 β-cells were performed using a doxycycline-inducible model. Interestingly, overexpression of p27 for 16 weeks in β-cells from adult mice had no effect on glucose tolerance, β-cell mass, or proliferation. In contrast, induction of p27 expression during β-cell development or early neonatal period resulted in severe glucose intolerance and reduced β-cell mass by decreased proliferation. These changes were reversible upon discontinuation of doxycycline. These experiments suggest that p27 is a critical molecule for β-cell proliferation during β-cell development and early postnatal life but not for maintenance of adult mass. Diabetes 55:3520-3528, 2006
- Subjects
CELL cycle; CELL proliferation; INSULIN resistance; CELL differentiation; LABORATORY mice
- Publication
Diabetes, 2006, Vol 55, Issue 12, p3520
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db06-0861