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Diabetes 54:2557-2567, 2005
© 2005 by the American Diabetes Association, Inc.
Very Slow Turnover of ß-Cells in Aged Adult Mice
1 Division of Endocrinology, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
2 Division of Endocrinology, Children’s Hospital, Boston, Harvard Medical School, Boston, Massachusetts
Although many signaling pathways have been shown to promote ß-cell growth, surprisingly little is known about the normal life cycle of preexisting ß-cells or the signaling pathways required for ß-cell survival. Adult ß-cells have been speculated to have a finite life span, with ongoing adult ß-cell replication throughout life to replace lost cells. However, little solid evidence supports this idea. To more accurately measure adult ß-cell turnover, we performed continuous long-term labeling of proliferating cells with the DNA precursor analog 5-bromo-2-deoxyuridine (BrdU) in 1-year-old mice. We show that ß-cells of aged adult mice have extremely low rates of replication, with minimal evidence of turnover. Although some pancreatic components acquired BrdU label in a linear fashion, only 1 in 
1,400 adult ß-cells were found to undergo replication per day. We conclude that adult ß-cells are very long lived.
Address correspondence and reprint requests to Jake A. Kushner, MD, Division of Endocrinology, Children’s Hospital of Philadelphia, 3615 Civic Center Blvd., Philadelphia, PA 19104. E-mail: kushnerj{at}mail.med.upenn.edu
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