title: G0-G1 transition and the restriction point in pancreatic β-cells in vivo.
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.
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Ayat
authors.initials: A
authors.lastname: Hija
authors.forename: Seth
authors.initials: S
authors.lastname: Salpeter
authors.forename: Agnes
authors.initials: A
authors.lastname: Klochendler
authors.forename: Joseph
authors.initials: J
authors.lastname: Grimsby
authors.forename: Michael
authors.initials: M
authors.lastname: Brandeis
authors.forename: Benjamin
authors.initials: B
authors.lastname: Glaser
authors.forename: Yuval
authors.initials: Y
authors.lastname: Dor
mesh_terms: D000818:Animals; D016193:G1 Phase / Q000502:physiology*; D005941:Glucokinase; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016192:Resting Phase, Cell Cycle / Q000502:physiology*; D016196:S Phase / Q000502:physiology
chemical_list: D005941:Glucokinase