Differential effects of p27 in regulation of β-cell mass during development, neonatal period, and adult life

Latif Rachdi, Norman Balcazar, Lynda Elghazi, Daniel J. Barker, Irina Krits, Hiroaki Kiyokawa, Ernesto Bernal-Mizrachi*

*Corresponding author for this work

Research output: Contribution to journalArticle

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3520-3528
Number of pages9
JournalDiabetes
Volume55
Issue number12
DOIs
StatePublished - Dec 1 2006

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Rachdi, L., Balcazar, N., Elghazi, L., Barker, D. J., Krits, I., Kiyokawa, H., & Bernal-Mizrachi, E. (2006). Differential effects of p27 in regulation of β-cell mass during development, neonatal period, and adult life. Diabetes, 55(12), 3520-3528. https://doi.org/10.2337/db06-0861