title: Glucose regulates rat beta cell number through age-dependent effects on beta cell survival and proliferation.
abstract: BACKGROUND
  Glucose effects on beta cell survival and DNA-synthesis suggest a role as regulator of beta cell mass but data on beta cell numbers are lacking. We examined outcome of these influences on the number of beta cells isolated at different growth stages in their population.
  
  
  METHODS
  Beta cells from neonatal, young-adult and old rats were cultured serum-free for 15 days. Their number was counted by automated whole-well imaging distinguishing influences on cell survival and on proliferative activity.
  
  
  RESULTS
  Elevated glucose (10-20 versus 5 mmol/l) increased the number of living beta cells from 8-week rats to 30%, following a time- and concentration-dependent recruitment of quiescent cells into DNA-synthesis; a glucokinase-activator lowered the threshold but did not raise total numbers of glucose-recruitable cells. No glucose-induced increase occurred in beta cells from 40-week rats. Neonatal beta cells doubled in number at 5 mmol/l involving a larger activated fraction that did not increase at higher concentrations; however, their higher susceptibility to glucose toxicity at 20 mmol/l resulted in 20% lower living cell numbers than at start. None of the age groups exhibited a repetitively proliferating subpopulation.
  
  
  CONCLUSIONS
  Chronically elevated glucose levels increased the number of beta cells from young-adult but not from old rats; they interfered with expansion of neonatal beta cells and reduced their number. These effects are attributed to age-dependent differences in basal and glucose-induced proliferative activity and in cellular susceptibility to glucose toxicity. They also reflect age-dependent variations in the functional heterogeneity of the rat beta cell population.
authors.affiliation: Diabetes Pathology and Therapy Unit, Diabetes Research Center and Center for Beta Cell Therapy, Brussels Free University-VUB, Brussels, Belgium.
authors.forename: Zerihun
authors.initials: Z
authors.lastname: Assefa
authors.affiliation: Diabetes Pathology and Therapy Unit, Diabetes Research Center and Center for Beta Cell Therapy, Brussels Free University-VUB, Brussels, Belgium.
authors.forename: Astrid
authors.initials: A
authors.lastname: Lavens
authors.affiliation: Diabetes Pathology and Therapy Unit, Diabetes Research Center and Center for Beta Cell Therapy, Brussels Free University-VUB, Brussels, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Steyaert
authors.affiliation: Diabetes Pathology and Therapy Unit, Diabetes Research Center and Center for Beta Cell Therapy, Brussels Free University-VUB, Brussels, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Stangé
authors.affiliation: Diabetes Pathology and Therapy Unit, Diabetes Research Center and Center for Beta Cell Therapy, Brussels Free University-VUB, Brussels, Belgium.
authors.forename: Geert A
authors.initials: GA
authors.lastname: Martens
authors.affiliation: Diabetes Pathology and Therapy Unit, Diabetes Research Center and Center for Beta Cell Therapy, Brussels Free University-VUB, Brussels, Belgium.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Ling
authors.affiliation: Diabetes Pathology and Therapy Unit, Diabetes Research Center and Center for Beta Cell Therapy, Brussels Free University-VUB, Brussels, Belgium.
authors.forename: Karine
authors.initials: K
authors.lastname: Hellemans
authors.affiliation: Diabetes Pathology and Therapy Unit, Diabetes Research Center and Center for Beta Cell Therapy, Brussels Free University-VUB, Brussels, Belgium.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pipeleers
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D057054:Molecular Imaging; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C476008:RO-28-0450; D013844:Thiazoles; D004247:DNA; D005941:Glucokinase; D005947:Glucose