title: Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture.
abstract: To explore the effect of fluctuating glucose on endothelial cells, human umbilical vein endothelial cells were incubated for 14 days in media containing different glucose concentrations: 5 mmol/l, 20 mmol/l, or a daily alternating 5 or 20 mmol/l glucose. Apoptosis was studied by different methods: viability assay, cell cycle analysis, DNA fragmentation, and morphological analysis. Furthermore, the levels of Bcl-2 and Bax, well known proteins involved in apoptosis, were evaluated. Stable high glucose induced apoptosis in human umbilical vein endothelial cells, a phenomenon accompanied by a significant decrease of Bcl-2 and a simultaneous increase of Bax expression. However, apoptosis was enhanced in human umbilical vein endothelial cells exposed to intermittent, rather than constant, high glucose concentration. In this condition, Bcl-2 was not detectable, whereas Bax expression was significantly enhanced. These findings suggest that variability in glycemic control could be more deleterious to endothelial cells than a constant high concentration of glucose.
authors.affiliation: Department of Science and Biomedical Technology, University of Udine, 33100 Udine, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Risso
authors.forename: F
authors.initials: F
authors.lastname: Mercuri
authors.forename: L
authors.initials: L
authors.lastname: Quagliaro
authors.forename: G
authors.initials: G
authors.lastname: Damante
authors.forename: A
authors.initials: A
authors.lastname: Ceriello
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle; D002470:Cell Survival; D002478:Cells, Cultured; D053938:DNA Fragmentation; D004587:Electrophoresis, Agar Gel; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism; D014471:Umbilical Veins; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D005947:Glucose