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.
journal_name
Diabetesjournal_title
Diabetesauthors
Rachdi L,Balcazar N,Elghazi L,Barker DJ,Krits I,Kiyokawa H,Bernal-Mizrachi Edoi
10.2337/db06-0861subject
Has Abstractpub_date
2006-12-01 00:00:00pages
3520-8issue
12eissn
0012-1797issn
1939-327Xpii
55/12/3520journal_volume
55pub_type
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