G0-G1 Transition and the Restriction Point in Pancreatic β-Cells In Vivo
- Ayat Hija1,
- Seth Salpeter1,
- Agnes Klochendler1,
- Joseph Grimsby2,
- Michael Brandeis3,
- Benjamin Glaser4 and
- Yuval Dor1⇑
- 1Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem, Israel
- 2Department of Metabolic Diseases, Hoffmann-La Roche, Nutley, NJ
- 3Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
- 4Endocrinology and Metabolism Service, Department of Internal Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
- Corresponding author: Yuval Dor, .
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 β-cells, a largely quiescent population, using drugs that mimic or prevent glucose-induced replication of β-cells in mice. Quiescent β-cells exposed to a mitogenic glucose stimulation require 8 h to enter the G1 phase of the cell cycle, and this time is prolonged in older age. The duration of G1, S, and G2/M is ∼5, 8, and 6 h, respectively. We further provide the first in vivo demonstration of the restriction point at the G0-G1 transition, discovered by Arthur Pardee 40 years ago. The findings may have pharmacodynamic implications in the design of regenerative therapies aimed at increasing β-cell replication and mass in patients with diabetes.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-1035/-/DC1.
- Received August 2, 2012.
- Accepted October 7, 2013.
- © 2014 by the American Diabetes Association.
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