Regulated β-Cell Regeneration in the Adult Mouse Pancreas

  1. Matthias Hebrok1
  1. 1Diabetes Center, University of California San Francisco, San Francisco, California
  2. 2Comprehensive Cancer Center, University of California San Francisco, San Francisco, California
  3. 3Biological Sciences, University of Warwick, Coventry, U.K
  1. Address correspondence and reprint requests to Jeffrey A. Bluestone, jbluest{at}diabetes.ucsf.edu, or Matthias Hebrok, mhebrok{at}diabetes.ucsf.edu

Abstract

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. 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. 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. 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.

  • Received July 4, 2007.
  • Accepted December 3, 2007.
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  1. Diabetes vol. 57 no. 4 958-966
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