Journal
DIABETES
Volume 63, Issue 2, Pages 578-584Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db12-1035
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Funding
- Juvenile Diabetes Research Foundation
- National Institutes of Health (Beta Cell Biology Consortium)
- Israel Cancer Research Fund (Barbara Goodman PC-RCDA)
- European Union (European Research Council) [241883]
- Leona M. and Harry B. Helmsley Charitable Trust
- Dutch Friends of Hebrew University
- I-CORE Program of the Planning and Budgeting Committee
- Israel Science Foundation [41.11]
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Most of our knowledge on cell kinetics stems from in vitro studies of continuously dividing cells. In this study, we determine in vivo cell-cycle parameters of pancreatic -cells, a largely quiescent population, using drugs that mimic or prevent glucose-induced replication of -cells in mice. Quiescent -cells exposed to a mitogenic glucose stimulation require 8 h to enter the G(1) phase of the cell cycle, and this time is prolonged in older age. The duration of G(1), S, and G(2)/M is approximate to 5, 8, and 6 h, respectively. We further provide the first in vivo demonstration of the restriction point at the G(0)-G(1) transition, discovered by Arthur Pardee 40 years ago. The findings may have pharmacodynamic implications in the design of regenerative therapies aimed at increasing -cell replication and mass in patients with diabetes.
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