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• W1983251003 abstract "Under normal conditions, the regeneration of mouse beta cells is mainly dependent on their own duplication. Although there is evidence that pancreatic progenitor cells exist around duct, whether non-beta cells in the islet could also potentially contribute to beta cell regeneration in vivo is still controversial. Here, we developed a novel transgenic mouse model to study the pancreatic beta cell regeneration, which could specifically inhibit beta cell proliferation by overexpressing p21(cip) in beta cells via regulation of the Tet-on system. We discovered that p21 overexpression could inhibit beta-cell duplication in the transgenic mice and these mice would gradually suffer from hyperglycemia. Importantly, the recovery efficiency of the p21-overexpressing mice from streptozotocin-induced diabetes was significantly higher than control mice, which is embodied by better physiological quality and earlier emergence of insulin expressing cells. Furthermore, in the islets of these streptozotocin-treated transgenic mice, we found a large population of proliferating cells which expressed pancreatic duodenal homeobox 1 (PDX1) but not markers of terminally differentiated cells. Transcription factors characteristic of early pancreatic development, such as Nkx2.2 and NeuroD1, and pancreatic progenitor markers, such as Ngn3 and c-Met, could also be detected in these islets. Thus, our work showed for the first time that when beta cell self-duplication is repressed by p21 overexpression, the markers for embryonic pancreatic progenitor cells could be detected in islets, which might contribute to the recovery of these transgenic mice from streptozotocin-induced diabetes. These discoveries could be important for exploring new diabetes therapies that directly promote the regeneration of pancreatic progenitors to differentiate into islet beta cells in vivo." @default.
• W1983251003 created "2016-06-24" @default.
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• W1983251003 date "2009-12-17" @default.
• W1983251003 modified "2023-09-26" @default.
• W1983251003 title "P21cip-Overexpression in the Mouse β Cells Leads to the Improved Recovery from Streptozotocin-Induced Diabetes" @default.
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• W1983251003 doi "https://doi.org/10.1371/journal.pone.0008344" @default.
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