Myo-inositol enhances the proliferation of human endothelial cells in culture but fails to prevent the delay induced by high glucose.
Evidence is accumulating, indicating that the abnormal metabolic milieu of diabetes might interfere with orderly replication of some cellular systems and in vitro studies point to a causal contribution of elevated glucose. We had previously shown that human umbilical vein endothelial cells cultured in 20 mmol/L glucose are delayed in achieving saturation density primarily as a consequence of decreased cellular proliferation. We have now addressed whether depletion of myo-inositol--a prevailing consequence of hyperglycemia in other tissues and overcome by provision of supplemental inositol--might play a role in the observed replicative abnormality. Control cultures (5 mmol/L glucose) displayed a dose-dependent response to myo-inositol supplementation that was maximal at concentrations (40 mumol/L) matching physiologic serum levels. The increment in cell number was (mean +/- SD) 141 +/- 20% of control (P less than 0.001), and saturation density was achieved at a cell number 160% higher than in nonsupplemented cultures. Thymidine incorporation and cell cycle studies documented that myo-inositol increased the number of cells cycle studies documented that myo-inositol increased the number of cells engaged in DNA synthesis. These effects of myo-inositol, as well as the dose-response relationship between ambient inositol levels and increments in cell number, were not significantly modified by 20 mmol/L glucose with the exceptions of a transient lesser effect of the physiologic doses during rapid proliferation (day 6) and a larger effect of all doses of myo-inositol in later stages of growth curve (day 12).(ABSTRACT TRUNCATED AT 250 WORDS)
D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000166:cytology* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007294:Inositol / Q000494:pharmacology / Q000502:physiology*; D014471:Umbilical Veins
D007294:Inositol; D005947:Glucose