The effect of elevated glucose levels on myo-inositol metabolism in cultured bovine aortic endothelial cells.
Bovine aorta endothelial cells were used to determine the effect of high ambient glucose concentrations on myo-inositol metabolism. Culturing the cells for a minimum of 1 week in elevated glucose concentrations caused an increase in the intracellular sorbitol content and a decrease in myo-inositol levels. The accumulation of myo-inositol from the medium and incorporation into phospholipids was reduced 25% to 50% in cells grown in the presence of 30 to 50 mmol/L glucose. This effect was not observed following a short-term exposure of the cells to elevated glucose levels. Kinetic analysis of high-affinity myo-inositol uptake showed that the K'm was significantly increased in cells grown in 30 mmol/L glucose compared to those cultured in 5.6 mmol/L glucose. This would suggest that exposing endothelial cells to high ambient glucose levels for a minimum of 1 week leads to a competitive type of inhibition of high-affinity myo-inositol uptake. The changes in myo-inositol metabolism and content and sorbitol levels mediated by glucose exposure were blocked by addition of the aldose reductase inhibitor, sorbinil, to the media, suggesting that these changes are caused by the accumulation of sorbitol by the cells. Exposure of bovine aorta endothelial cells to high ambient levels of glucose leads to accumulation of sorbitol in the cells, which is responsible for alterations in myo-inositol metabolism. These changes could result in alteration of endothelial cell membrane function and contribute to the pathology of diabetes mellitus.
Yorek
M A
MA
Department of Internal Medicine, Diabetes Endocrinology Research Center, Iowa City, IA.
Dunlap
J A
JA
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007294:Inositol / Q000378:metabolism*; D007700:Kinetics; D010743:Phospholipids / Q000096:biosynthesis; D013012:Sorbitol / Q000378:metabolism
D007093:Imidazoles; D048289:Imidazolidines; D010743:Phospholipids; D007294:Inositol; D013012:Sorbitol; D000449:Aldehyde Reductase; C026411:sorbinil; D005947:Glucose