Effect of increased glucose levels on Na+/K+-pump activity in cultured neuroblastoma cells.
Neuroblastoma cells were used to analyze the effect of elevated glucose levels on myo-inositol metabolism and Na+/K+-pump activity. The activity of the Na+/K+ pump in neuroblastoma cells is almost totally sensitive to ouabain inhibition. Culturing neuroblastoma cells in 30 mM glucose caused a significant decrease in Na+/K+-pump activity, myo-inositol metabolism, and myo-inositol content, compared to cells grown in the presence of 30 mM fructose. Glucose supplementation also caused a large intracellular accumulation of sorbitol. The aldose reductase inhibitor sorbinil prevented the abnormalities in myo-inositol metabolism and partially restored Na+/K+-pump activity in neuroblastoma cells cultured in the presence of elevated glucose levels. These results suggest that the accumulation of sorbitol by neuroblastoma cells exposed to elevated concentrations of extracellular glucose causes a decrease in myo-inositol metabolism and these abnormalities are associated with a reduction in Na+/K+-pump activity.
Yorek
M A
MA
Veterans Administration Medical Center, Department of Internal Medicine, Iowa City, IA 52240.
Dunlap
J A
JA
Ginsberg
B H
BH
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D002460:Cell Line; D005947:Glucose / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007294:Inositol / Q000378:metabolism; D051379:Mice; D009447:Neuroblastoma / Q000201:enzymology*; D012413:Rubidium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D007093:Imidazoles; D048289:Imidazolidines; D007294:Inositol; D000449:Aldehyde Reductase; D000254:Sodium-Potassium-Exchanging ATPase; C026411:sorbinil; D005947:Glucose; D012413:Rubidium