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Regulated beta-cell regeneration in the adult mouse pancreas

By David A. Cano, Ingrid C. Rulifson, Patrick W. Heiser, Lamorna B. Swigart, Stella Pelengaris, Mike German, Gerard I. Evan, Jeffrey A. Bluestone and Matthias Hebrok

Abstract

Several studies have shown that the adult pancreas possesses a limited potential for beta-cell regeneration upon tissue injury. One of the difficulties in studying P-cell regeneration has been the lack of a robust, synchronized animal model system that would allow controlled regulation of beta-cell loss and subsequent proliferation in adult pancreas. Here we present a transgenic mouse regeneration model in which the c-Myc transcription factor/mutant estrogen receptor (cMycER(TAM)) fusion protein can be specifically activated in mature P-cells. We have studied these transgenic mice by immunohistochemical and biochemical methods to assess the ablation and posterior regeneration of P-cells. Activation of the cMycER(TAM) fusion protein results in synchronous and selective P-cell apoptosis followed by the onset of acute diabetes. Inactivation of c-Myc leads to gradual regeneration of insulin-expressing cells and reversal of diabetes. Our results demonstrate that the mature pancreas has the ability to fully recover from almost complete ablation of all existing beta-cells. Our results also suggest the regeneration of beta-cells is mediated by replication of P-cells rather than neogenesis from pancreatic ducts

Topics: QH301, QP
Publisher: American Diabetes Association
Year: 2008
OAI identifier: oai:wrap.warwick.ac.uk:30303
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