Moss, J.B., Koustubhan, P., Greenman, M., Parsons, M.J., Walter, I., and Moss, L.G. (2009) Regeneration of the Pancreas in Adult Zebrafish. Diabetes. 58(8):1844-1851.
OBJECTIVE- Regenerating organs in diverse biological systems have provided clues to processes that can be harnessed to repair damaged tissue. Adult mammalian beta cells have a limited capacity to regenerate, resulting in diabetes and lifelong reliance on insulin. Zebrafish have been used as a model for the regeneration of many organs. We demonstrate the regeneration of adult zebrafish pancreatic beta cells. This non-mammalian model can be used to define pathways for islet cell regeneration in humans. RESEARCH DESIGN AND METHODS- Adult transgenic zebrafish were injected with a single high dose of streptozotocin or metronidazole and sacrificed at 3, 7 or 14 days or pancreatectomized. Blood glucose measurements were determined and gut sections were analyzed using specific endocrine, exocrine and duct cell markers as well as markers for dividing cells. RESULTS- Zebrafish recovered rapidly without the need for insulin injections and normoglycemia was attained within two weeks. Although few proliferating cells were present in vehicles, ablation caused islet destruction and a striking increase of proliferating cells, some of which were Pdx1 positive. Dividing cells were primarily associated with affected islets and ducts, but with the exception of surgical partial pancreatectomy, were not extensively beta cells. CONCLUSIONS- The ability of the zebrafish to regenerate a functional pancreas using chemical, genetic and surgical approaches enabled us to identify patterns of cell proliferation in islets and ducts. Further study of the origin and contribution of proliferating cells in re-establishing islet function could provide strategies for treating human diseases.