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Insulin Signaling Regulates the FoxM1/PLK1/CENP-A Pathway to Promote Adaptive Pancreatic β Cell Proliferation.
- Source :
- Cell Metabolism; Apr2017, Vol. 25 Issue 4, p868-882.e5, 1p
- Publication Year :
- 2017
-
Abstract
- Summary Investigation of cell-cycle kinetics in mammalian pancreatic β cells has mostly focused on transition from the quiescent (G0) to G1 phase. Here, we report that centromere protein A (CENP-A), which is required for chromosome segregation during the M-phase, is necessary for adaptive β cell proliferation. Receptor-mediated insulin signaling promotes DNA-binding activity of FoxM1 to regulate expression of CENP-A and polo-like kinase-1 (PLK1) by modulating cyclin-dependent kinase-1/2. CENP-A deposition at the centromere is augmented by PLK1 to promote mitosis, while knocking down CENP-A limits β cell proliferation and survival. CENP-A deficiency in β cells leads to impaired adaptive proliferation in response to pregnancy, acute and chronic insulin resistance, and aging in mice. Insulin-stimulated CENP-A/PLK1 protein expression is blunted in islets from patients with type 2 diabetes. These data implicate the insulin-FoxM1/PLK1/CENP-A pathway-regulated mitotic cell-cycle progression as an essential component in the β cell adaptation to delay and/or prevent progression to diabetes. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15504131
- Volume :
- 25
- Issue :
- 4
- Database :
- Supplemental Index
- Journal :
- Cell Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 122290057
- Full Text :
- https://doi.org/10.1016/j.cmet.2017.02.004