title: CCCTC-binding factor mediates effects of glucose on beta cell survival.
abstract: OBJECTIVE
  Pancreatic islet β-cell survival is paramount for regulation of insulin activity and for maintaining glucose homeostasis. Recently, Pax6 has been shown to be essential for many vital functions in β-cells, although many molecular mechanisms of its homeostasis in β-cells remain unclear. The present study investigates novel effects of glucose- and insulin-induced CCCTC-binding factor (CTCF) activity on Pax6 gene expression as well as for subsequent effects of insulin-activated signalling pathways, on β-cell proliferation.
  
  
  METHODS
  Pancreatic β-TC-1-6 cells were cultured in DMEM and stimulated with high concentrations of glucose (5-125 mm); cell viability was assessed by MTT assay. Effects of CTCF on Pax6 were evaluated in the high glucose-induced environment and CTCF/Erk-suppressed cells, by promoter reporter and western blotting analyses.
  
  
  RESULTS
  Increases in glucose and insulin concentrations upregulated CTCF and consequently downregulated Pax6 in β-cell survival and proliferation. Knocking-down CTCF directly affected Pax6 transcription through CTCF binding and blocked the response to glucose. Altered Erk activity mediated effects of CTCF on controlling Pax6 expression, which partially regulated β-cell proliferation.
  
  
  CONCLUSIONS
  CTCF functioned as a molecular mediator between insulin-induced upstream Erk signalling and Pax6 expression in these pancreatic β-cells. This pathway may contribute to regulation of β-cell survival and proliferation.
authors.affiliation: Department of Medicine, David Geffen School of Medicine University of California Los Angeles, Torrance, CA, 90502, USA.
authors.forename: S
authors.initials: S
authors.lastname: Tsui
authors.forename: W
authors.initials: W
authors.lastname: Dai
authors.forename: L
authors.initials: L
authors.lastname: Lu
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005136:Eye Proteins / Q000235:genetics; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D007763:Lac Operon; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000076246:CCCTC-Binding Factor; C000619698:Ctcf protein, mouse; D005136:Eye Proteins; D018398:Homeodomain Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D005947:Glucose