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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

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Official URL: http://dx.doi.org/10.2337/db07-0913

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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
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:
DateEvent
April 2008Published
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)

Data sourced from Thomson Reuters' Web of Knowledge

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