title: Myo-inositol enhances the proliferation of human endothelial cells in culture but fails to prevent the delay induced by high glucose.
abstract: 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)
mesh_terms: 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
chemical_list: D007294:Inositol; D005947:Glucose