Restoration of Na(+)-K+ pump activity and resting membrane potential by myo-inositol supplementation in neuroblastoma cells chronically exposed to glucose or galactose

Mark A Yorek; Joyce A Dunlap; Mark R Stefani

doi:10.2337/diab.40.2.240

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Restoration of Na(+)-K+ pump activity and resting membrane potential by myo-inositol supplementation in neuroblastoma cells chronically exposed to glucose or galactose

Journal article

Peer reviewed

Restoration of Na(+)-K+ pump activity and resting membrane potential by myo-inositol supplementation in neuroblastoma cells chronically exposed to glucose or galactose

Mark A Yorek, Joyce A Dunlap and Mark R Stefani

Diabetes (New York, N.Y.), Vol.40(2), pp.240-248

02/1991

DOI: 10.2337/diab.40.2.240

PMID: 1846827

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Abstract

myo-Inositol uptake by culture neuroblastoma cells at a concentration of myo-inositol less than 50 microM was largely Na+ dependent. Exposing neuroblastoma cells to media supplemented with increasing concentrations of myo-inositol resulted in an increase in myo-inositol accumulation and intracellular content, but myo-inositol incorporation into phospholipids was not increased. The data indicate that myo-inositol exists as separate pools in neuroblastoma cells, and one or more of these pools may contribute to phospholipid synthesis. Exposing neuroblastoma cells to an increased concentration of glucose caused a decrease in myo-inositol uptake by two separate mechanisms. Acute exposure of the cells to 30 mM glucose caused a myo-inositol concentration-dependent decrease in Na(+)-dependent myo-inositol uptake. We propose that the acute inhibition of myo-inositol uptake by glucose is likely due to a competitive type of inhibition. Chronic exposure of cells to media containing 30 mM glucose or 30 mM galactose also caused decreases in myo-inositol uptake and incorporation into inositol phospholipids and intracellular myo-inositol content. This decrease in myo-inositol metabolism persisted at a higher concentration of external myo-inositol than the acute inhibition. Supplementing media containing 30 mM glucose or 30 mM galactose with 250 microM myo-inositol restored myo-inositol metabolism and content. The inhibition of myo-inositol uptake by cells chronically exposed to increased concentrations of glucose or galactose was due to a noncompetitive type of inhibition that was blocked by the addition of sorbinil. Chronic exposure of neuroblastoma cells to media containing 30 mM glucose or 30 mM galactose caused a decrease in Na(+)-K(+)-ATPase transport activity and resting membrane potential.

Membrane Potentials - drug effects

Potassium - metabolism

Inositol - pharmacology

Galactose - pharmacology

Inositol - metabolism

Biological Transport, Active - drug effects

Glucose - pharmacology

Sodium - metabolism

Cell Membrane - physiology

Membrane Potentials - physiology

Potassium - pharmacokinetics

Dose-Response Relationship, Drug

Sodium-Potassium-Exchanging ATPase - metabolism

Neuroblastoma - physiopathology

Animals

Biological Transport, Active - physiology

Culture Media

Cell Membrane - metabolism

Mice

Neuroblastoma - metabolism

Sodium - pharmacokinetics

Phospholipids - metabolism

Tumor Cells, Cultured

Cell Membrane - drug effects

Details

Title: Subtitle: Restoration of Na(+)-K+ pump activity and resting membrane potential by myo-inositol supplementation in neuroblastoma cells chronically exposed to glucose or galactose
Creators: Mark A Yorek - Department of Internal Medicine, Veterans Administration Medical Center, Iowa City, IA 52246
Joyce A Dunlap
Mark R Stefani
Resource Type: Journal article
Publication Details: Diabetes (New York, N.Y.), Vol.40(2), pp.240-248
DOI: 10.2337/diab.40.2.240
PMID: 1846827
ISSN: 0012-1797
eISSN: 1939-327X
Grant note: AM-25295 / NIADDK NIH HHS NS-23785 / NINDS NIH HHS
Language: English
Date published: 02/1991
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094657402771

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