G₀-G₁ 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 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-Cells replication and mass in patients with diabetes.