Evaluation of gliclazide ability to attenuate the hyperglycaemic 'memory' induced by high glucose in isolated human endothelial cells
Corgnali, Maddalena, Piconi, Ludovica, Ihnat, Michael and Ceriello, Antonio. (2008) Evaluation of gliclazide ability to attenuate the hyperglycaemic 'memory' induced by high glucose in isolated human endothelial cells. Diabetes - Metabolism: Research and Reviews, Vol.24 (No.4). pp. 301-309. ISSN 1520-7552Full text not available from this repository.
Official URL: http://dx.doi.org/10.1002/dmrr.804
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 mu mol/L) and glibenclamide (1 mu mol/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. Copyright (C) 2007 John Wiley & Sons, Ltd.
|Item Type:||Journal Article|
|Subjects:||Q Science > QP Physiology
R Medicine > RB Pathology
|Divisions:||Faculty of Medicine > Warwick Medical School|
|Library of Congress Subject Headings (LCSH):||Hyperglycemia, Endothelial cells, Oxidative stress, Gliclazide|
|Journal or Publication Title:||Diabetes - Metabolism: Research and Reviews|
|Publisher:||John Wiley & Sons Ltd|
|Official Date:||May 2008|
|Number of Pages:||9|
|Page Range:||pp. 301-309|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Servier Research Institute|
1. Brownlee M. Biochemistry and molecular cell biology of diabetic
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