Very slow turnover of beta-cells in aged adult mice.
Although many signaling pathways have been shown to promote beta-cell growth, surprisingly little is known about the normal life cycle of preexisting beta-cells or the signaling pathways required for beta-cell survival. Adult beta-cells have been speculated to have a finite life span, with ongoing adult beta-cell replication throughout life to replace lost cells. However, little solid evidence supports this idea. To more accurately measure adult beta-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 beta-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 approximately 1,400 adult beta-cells were found to undergo replication per day. We conclude that adult beta-cells are very long lived.
Teta
Monica
M
Division of Endocrinology, Children's Hospital of Philadelphia, 3615 Civic Center Blvd., Philadelphia, PA 19104, USA.
Long
Simon Y
SY
Wartschow
Lynn M
LM
Rankin
Matthew M
MM
Kushner
Jake A
JA
D000375:Aging / Q000502:physiology*; D000818:Animals; D001976:Bromouracil / Q000031:analogs & derivatives; D016923:Cell Death; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005934:Glucagon / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology* / Q000502:physiology*; D008297:Male; D051379:Mice; D010191:Pancreatic Polypeptide / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism; D013311:Streptozocin / Q000494:pharmacology; D014529:Uridine / Q000031:analogs & derivatives
D001976:Bromouracil; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D013311:Streptozocin; D005934:Glucagon; C006824:5-bromouridine; D014529:Uridine