Journal article
Acute and chronic exposure of mouse cerebral microvessel endothelial cells to increased concentrations of glucose and galactose: effect on myo-inositol metabolism, PGE2 synthesis, and Na+/K(+)-ATPase transport activity
Metabolism, clinical and experimental, Vol.40(4), pp.347-358
04/1991
DOI: 10.1016/0026-0495(91)90144-L
PMID: 1849218
Abstract
Cultured mouse cerebral microvessel endothelial cells have a large intracellular myo-inositol content and rapidly take up extracellular myo-inositol. Myo-inositol uptake occurs by a high- and low-affinity transport system. Both transport systems appear to be Na(+)-dependent. The high- and low-affinity transport systems have a Km of 11 and 198 mumol/L and a Vmax of 47 and 381 pmol/min/mg protein, respectively. Acute exposure of cultured cells to 30 mmol/L D-glucose or D-galactose causes a decrease in myo-inositol uptake. The acute effect of glucose and galactose on myo-inositol uptake is sensitive to the extracellular myo-inositol concentration. The acute effect of glucose is apparently due to a competitive inhibition of high-affinity myo-inositol transport and has a Ki of 21 mmol/L. L-Glucose is more effective than D-glucose in decreasing myo-inositol uptake. In contrast, 2-deoxyglucose or 3-0-methylglucose does not acutely inhibit myo-inositol uptake. This suggests that the hydroxyl groups on carbons 2 and 3 of glucose are necessary for inhibitory activity. Chronic exposure of cells to media containing 136.4 mumol/L myo-inositol and 30 mmol/L glucose has no effect on myo-inositol accumulation from the extracellular fluid, myo-inositol incorporation into inositol phospholipids, or total myo-inositol content. Chronic exposure of the cells to media containing 30 mmol/L glucose causes only a small increase in the intracellular sorbitol content. In contrast, chronic exposure of the cells to media containing 30 mmol/L galactose causes a large increase in galactitol content and a decrease in myo-inositol accumulation, myo-inositol incorporation into inositol phospholipids, and intracellular myo-inositol content. Sorbinil treatment of the galactose-supplemented media protects the cells form changes in myo-inositol metabolism and content. Chronic exposure of the cells to media containing 30 mmol/L glucose or 30 mmol/L galactose causes a decrease in ouabain-sensitive Na+/K(+)-ATPase transport activity, which is corrected by the addition of sorbinil to the media. Chronic exposure of the cells to media containing 45 mmol/L glucose, but not galactose, causes an increase in PGE2 production. These studies suggest that acute or chronic exposure of cultured microvessel endothelial cells to increased concentrations of glucose or galactose causes a decrease in myo-inositol uptake by different mechanisms. Chronic exposure of the cells to increased concentrations of glucose or galactose causes alterations in endothelial cell properties, including Na+/K(+)-ATPase transport activity and eicosanoid synthesis. The data are not clearly supportive of polyol accumulation and myo-inositol depletion as being responsible for the decrease in Na+/K+ pump activity.
Details
- Title: Subtitle
- Acute and chronic exposure of mouse cerebral microvessel endothelial cells to increased concentrations of glucose and galactose: effect on myo-inositol metabolism, PGE2 synthesis, and Na+/K(+)-ATPase transport activity
- Creators
- Mark A Yorek - Department of Internal Medicine and Pathology, Veterans Administration Medical Center, Iowa City, IA 52246Mark R StefaniSteven A Moore
- Resource Type
- Journal article
- Publication Details
- Metabolism, clinical and experimental, Vol.40(4), pp.347-358
- Publisher
- United States
- DOI
- 10.1016/0026-0495(91)90144-L
- PMID
- 1849218
- ISSN
- 0026-0495
- eISSN
- 1532-8600
- Grant note
- NS 24621 / NINDS NIH HHS AM25295 / NIADDK NIH HHS NS 01096 / NINDS NIH HHS
- Language
- English
- Date published
- 04/1991
- Academic Unit
- Pathology; Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984047665102771
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