G0-G1 Transition and the Restriction Point in Pancreatic β-Cells In Vivo

  1. Yuval Dor1
  1. 1Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem, Israel
  2. 2Department of Metabolic Diseases, Hoffmann-La Roche, Nutley, NJ
  3. 3Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
  4. 4Endocrinology and Metabolism Service, Department of Internal Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  1. Corresponding author: Yuval Dor, yuvald{at}ekmd.huji.ac.il.

Abstract

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.

Footnotes

  • Received August 2, 2012.
  • Accepted October 7, 2013.

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  1. Diabetes vol. 63 no. 2 578-584
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