Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture

To explore the effect of fluctuating glucose on endothelial cells, human um bilical vein endothelial cells were incubated for 14 days in media containi ng different glucose concentrations: 5 mmol/l, 20 mmol/l, or a daily altern ating 5 or 20 mmol/l glucose. Apoptosis was studied by different methods: v iability assay, cell cycle analysis, DNA fragmentation, and morphological a nalysis. Furthermore, the levels of Bcl-2 and Bax, well known proteins invo lved in apoptosis, were evaluated. Stable high glucose induced apoptosis in human umbilical vein endothelial cells, a phenomenon accompanied by a sign ificant decrease of Bcl-2 and a simultaneous increase of Bax expression. Ho wever, apoptosis was enhanced in human umbilical vein endothelial cells exp osed to intermittent, rather than constant, high glucose concentration. In this condition, Bcl-2 was not detectable, whereas Bax expression was signif icantly enhanced. These findings suggest that variability in glycemic contr ol could be more deleterious to endothelial cells than a constant high conc entration of glucose.