title: Evaluation of gliclazide ability to attenuate the hyperglycaemic 'memory' induced by high glucose in isolated human endothelial cells.
abstract: BACKGROUND
  Patients with long-term exposure to high levels of hyperglycaemia remain more susceptible to diabetes-related complications, even with subsequent lower levels of hyperglycaemia. We sought to confirm the hypothesis that exposure to continuous increased glucose results in a memory of cellular stress in isolated endothelial cells, even when switched back to normal glucose, and to investigate the ability of gliclazide to attenuate this phenomenon.
  
  
  METHODS
  Human umbilical vein endothelial cells were incubated for 21 days in normal glucose (5 mmol/L), high glucose (30 mmol/L), or high glucose for 14 days followed by normal glucose for 7 days (memory condition). The effects of gliclazide (10 micromol/L) and glibenclamide (1 micromol/L) were evaluated in the memory condition and added to the culture media early (first 14 days), late (last 7 days), or throughout the study. Oxidative stress and cell apoptosis parameters were investigated.
  
  
  RESULTS
  Continuous high glucose increased reactive oxygen species, 8-OHdG, nitrotyrosine, caspase-3, and reduced Bcl-2 expression. These deleterious effects were also observed in the memory condition. Gliclazide applied early or throughout the study improved all parameters. In contrast, glibenclamide showed no relevant effect on study parameters.
  
  
  CONCLUSIONS
  Our results suggest that gliclazide prevents endothelial cell apoptosis by reducing oxidative stress. The results appear to confirm the hypothesis that exposure of cells to continuous increased glucose results in a hyperglycaemic cellular memory that remains, even when cells are switched back to normal glucose. Gliclazide attenuated this cellular memory, decreasing oxidative stress and protecting vascular endothelial cells from apoptosis.
authors: Morpurgo-Hofman Research Laboratory on Aging, Udine, Italy.
authors: Maddalena
authors: M
authors: Corgnali
authors: Ludovica
authors: L
authors: Piconi
authors: Michael
authors: M
authors: Ihnat
authors: Antonio
authors: A
authors: Ceriello
mesh_terms: D017209:Apoptosis; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D005907:Gliclazide / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000494:pharmacology; D018384:Oxidative Stress; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014471:Umbilical Veins
chemical_list: D007004:Hypoglycemic Agents; D011493:Protein Kinase C; D005907:Gliclazide; D005905:Glyburide