High glucose concentrations inhibit DNA synthesis and replication without causing death or impairing injury repair in cultured human endothelial cells.
Endothelial cells are directly exposed to the metabolic derangements of diabetes mellitus and may be damaged early, if not primitively, in the pathogenesis of diabetic microangiopathy. Cultured human umbilical vein endothelial cells were subjected to equimolar concentrations of glucose or mannitol for the evaluation of 3H-thymidine uptake, cell replication, cell death and repair of standard mechanical lesions. 3H-thymidine uptake was inhibited dose-dependently and to a similar extent by both glucose and mannitol. The former reduced cell replication whereas the latter did not (p less than 0.01 at 27.8 mmol/l, p less than 0.001 at 50.0 mmol/l). Neither caused excess cell death nor interfered with lesion repair. These results suggest that supra-physiological amounts of glucose inhibit DNA synthesis with osmotic mechanisms, delay cell replication through at least partially non osmotic effects, do not cause excess cell death and do not impair local injury repair. The above effects may play a role in the pathogenesis of long-term complications of diabetes.
D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008353:Mannitol / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D008353:Mannitol; D005947:Glucose; D013936:Thymidine