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Regulated beta-cell regeneration in the adult mouse pancreas
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Cano, David A., Rulifson, Ingrid C., Heiser, Patrick W., Swigart, Lamorna B., Pelengaris, Stella, German, Mike, Evan, Gerard I., Bluestone, Jeffrey A. and Hebrok, Matthias (2008) Regulated beta-cell regeneration in the adult mouse pancreas. Diabetes, Vol.57 (No.4). pp. 958-966. doi:10.2337/db07-0913 ISSN 0012-1797.
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Official URL: http://dx.doi.org/10.2337/db07-0913
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.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QP Physiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||
| Library of Congress Subject Headings (LCSH): | Mice -- Cytology, Pancreatic beta cells, Regeneration (Biology) | ||||
| Journal or Publication Title: | Diabetes | ||||
| Publisher: | American Diabetes Association | ||||
| ISSN: | 0012-1797 | ||||
| Official Date: | April 2008 | ||||
| Dates: |
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| Volume: | Vol.57 | ||||
| Number: | No.4 | ||||
| Number of Pages: | 9 | ||||
| Page Range: | pp. 958-966 | ||||
| DOI: | 10.2337/db07-0913 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | Sandler Family Supporting Foundation, Juvenile Diabetes Research Foundation (U.K.), University of California, San Francisco. Diabetes and Endocrinology Research Center, National Institutes of Health (U.S.) (NIH), California Institute for Regenerative Medicine | ||||
| Grant number: | 4-2004-372 (JDRF), P30-DK63720 (DERC), 5T32-A107334-13 (NIH) |
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