Regeneration of the pancreas in adult zebrafish.
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 nonmammalian model can be used to define pathways for islet-cell regeneration in humans.


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 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 reestablishing islet function could provide strategies for treating human diseases.
Moss
Jennifer B
JB
Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina, USA. jennifer.b.moss@duke.edu
Koustubhan
Punita
P
Greenman
Melanie
M
Parsons
Michael J
MJ
Walter
Ingrid
I
Moss
Larry G
LG
D000818:Animals; D030801:Animals, Genetically Modified; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D008954:Models, Biological; D010180:Pancreatectomy; D012016:Reference Values; D012038:Regeneration / Q000502:physiology*; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development / Q000502:physiology
D001786:Blood Glucose