Very Slow Turnover of β-Cells in Aged Adult Mice

Very Slow Turnover of β-Cells in Aged Adult Mice Monica Teta 1 , Simon Y. Long 1 , Lynn M. Wartschow 2 , Matthew M. Rankin 1 and Jake A. Kushner 1 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 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 Abstract Although many signaling pathways have been shown to promote β-cell growth, surprisingly little is known about the normal life cycle of preexisting β-cells or the signaling pathways required for β-cell survival. Adult β-cells have been speculated to have a finite life span, with ongoing adult β-cell replication throughout life to replace lost cells. However, little solid evidence supports this idea. To more accurately measure adult β-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 β-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 β-cells were found to undergo replication per day. We conclude that adult β-cells are very long lived. Footnotes BrdU, 5-bromo-2-deoxyuridine; DAPI, 4′,6 diamino-2-phenylindole; TUNEL, transferase-mediated dUTP nick-end labeling. 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. Accepted May 23, 2005. Received February 14, 2005. DIABETES