Regeneration of the Pancreas in Adult Zebrafish

• Published in: Diabetes (New York, N.Y.) Vol. 58; no. 8; pp. 1844 - 1851
• Main Authors: MOSS, Jennifer B, KOUSTUBHAN, Punita, GREENMAN, Melanie, PARSONS, Michael J, WALTER, Ingrid, MOSS, Larry G
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.08.2009
• Subjects: Ablation; Animal models in research; Animal research models; Animals; Animals, Genetically Modified; Biological and medical sciences; Blood Glucose - metabolism; Cell division; Cell growth; Cell proliferation; Diabetes; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Experimental - physiopathology; Diabetes. Impaired glucose tolerance; Drug dosages; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Genetic aspects; Glucose; Humans; Hyperglycemia; Insulin; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - pathology; Insulin-Secreting Cells - physiology; Medical sciences; Models, Biological; Original; Pancreas; Pancreatectomy; Pancreatic beta cells; Physiological aspects; Reference Values; Regeneration (Biology); Regeneration - physiology; Research design; Zebrafish; Zebrafish - genetics; Zebrafish - growth & development; Zebrafish - physiology; United States; Endocrinopathy; Regeneration; Pancreas; Diabetes mellitus
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db08-0628

Regeneration of the Pancreas in Adult Zebrafish Jennifer B. Moss 1 , Punita Koustubhan 2 , Melanie Greenman 1 , Michael J. Parsons 4 , Ingrid Walter 3 and Larry G. Moss 1 1 Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina; 2 Tufts Center for Regenerative and Developmental Biology, Tufts University, Medford, Massachusetts; 3 Department of Pathobiology, Institute of Anatomy, University of Veterinary Medicine, Vienna, Austria; 4 Department of Surgery, Johns Hopkins University, Baltimore, Maryland. Corresponding author: Jennifer B. Moss, jennifer.b.moss{at}duke.edu . Abstract OBJECTIVE Regenerating organs in diverse biological systems have provided clues to processes that can be harnessed to repair damaged tissue. Adult mammalian β-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 β-cells. This nonmammalian 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 anesthetized 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 2 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 β-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 reestablishing islet function could provide strategies for treating human diseases. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received May 9, 2008. Accepted May 14, 2009. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. © 2009 by the American Diabetes Association.