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Diabetes Publish Ahead of Print published online ahead of print December 14, 2007
DOI: 10.2337/db07-0913

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Original Research

Regulated β-cell regeneration in the adult mouse pancreas

David A. Cano1, Ingrid C. Rulifson1, Patrick W. Heiser1, Lamorna B. Swigart2, Stella Pelengaris3, Mike German1, Gerard I. Evan2, Jeffrey A. Bluestone1, and Matthias Hebrok1

1Diabetes Center
2Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143
3Biological Sciences, University of Warwick, Coventry CV4 7AL, UK

Objective: Several studies have shown that the adult pancreas possesses a limited potential for β–cell regeneration upon tissue injury. One of the difficulties in studying β-cell regeneration has been the lack of a robust, synchronized animal model system that would allow controlled regulation of β-cell loss and subsequent proliferation in adult pancreas.

Research Design and Methods: Here we present a transgenic mouse regeneration model in which the c–Myc transcription factor/mutant estrogen receptor (cMycERTAM) fusion protein can be specifically activated in mature β–cells. We have studied these transgenic mice by immunohistochemical and biochemical methods to assess the ablation and posterior regeneration of β-cells.

Results: Activation of the cMycERTAM fusion protein results in synchronous and selective β–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.

Conclusions: Our results demonstrate that the mature pancreas has the ability to fully recover from almost complete ablation of all existing β–cells. Our results also suggest the regeneration of β-cells is mediated by replication of β-cells rather than neogenesis from pancreatic ducts.


Correspondence: jbluest{at}diabetes.ucsf.edu

Correspondence: mhebrok{at}diabetes.ucsf.edu

Key Words: Islet • pancreas • regeneration • insulin


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