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Effect of Fructose Supplementation on Sorbitol Accumulation and myolnositol Metabolism in Cultured Neuroblastoma Cells Exposed to Increased Glucose Concentrations
Author(s) -
Yorek Mark A.,
Dunlap Joyce A.,
Leeney Ellen M.,
Stefani Mark R.
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb03148.x
Subject(s) - sorbitol , fructose , carbohydrate metabolism , metabolism , neuroblastoma , endocrinology , medicine , chemistry , biology , biochemistry , cell culture , genetics
Aldose reductase activity is increased in neuroblastoma cells grown in media containing 30 m M fructose and/or 30 m M glucose. Neuroblastoma cells cultured in media supplemented with increased concentrations of glucose and fructose amass greater amounts of sorbitol than do cells exposed to media containing only high glucose concentrations. The increase in sorbitol content is dependent on the fructose and glucose concentration in the media. The increase in sorbitol content caused by exposing neuroblastoma cells to media containing 30 m M glucose/30 m M fructose is due to a protein synthesis sensitive mechanism and not to an alteration in the redox state. The addition of sorbinil to media containing 30 m M glucose blocks the increase in sorbitol content. In contrast, sorbinil treatment of media containing 30 mM glucose/30 m M fructose does not totally block the increase in sorbitol levels, myo ‐lnositol accumulation and incorporation into inositol phospholipids and intracellular myo ‐inositol content are decreased in cells chronically exposed to media containing 30 m M glucose or 30 m M glucose/ 30 m M fructose compared to cells cultured in unsupplemented media or media containing 30 m M fructose. However, maximal depletion of myo ‐inositol accumulation and intracellular content occurs earlier in cells exposed to media containing 30 m M glucose/30 m M fructose than in cells exposed to media supplemented with 30 m M glucose. Sorbinil treatment of media containing 30 m M glucose/30 m M fructose maintains cellular myo ‐inositol accumulation and incorporation into phospholipids at near normal levels, myo ‐Inositol content in neuroblastoma cells chronically exposed to media containing 30 m M glucose or 30 m M glucose/30 m M fructose recovers within 72 h when the cells are transferred to unsupplemented media or media containing 30 m M fructose. In contrast, the sorbitol content of cells previously exposed to media containing 30 m M glucose or 30 m M glucose/30 m M fructose then transferred into media containing 30 m M fructose remains elevated compared to the sorbitol content of cells transferred into unsupplemented media. These data suggest that fructose may be activating or increasing sorbinil‐resistant aldose reductase activity as well as partially blocking sorbitol dehydrogenase activity. The presence of increased concentrations of fructose in combination with increased glucose levels may enhance alterations in cell metabolism and properties due to increased sorbitol levels.