G(0)-G(1) Transition and the Restriction Point in Pancreatic β-Cells In Vivo

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 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 ∼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 β-cell replication and mass in patients with diabetes.