Effect of galactose and glucose levels and sorbinil treatment on myo-inositol metabolism and Na+-K+ pump activity in cultured neuroblastoma cells

Mark A Yorek; Joyce A Dunlap; Ellen M Leeney

doi:10.2337/diab.38.8.996

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Effect of galactose and glucose levels and sorbinil treatment on myo-inositol metabolism and Na+-K+ pump activity in cultured neuroblastoma cells

Journal article

Peer reviewed

Effect of galactose and glucose levels and sorbinil treatment on myo-inositol metabolism and Na+-K+ pump activity in cultured neuroblastoma cells

Mark A Yorek, Joyce A Dunlap and Ellen M Leeney

Diabetes (New York, N.Y.), Vol.38(8), pp.996-1004

08/1989

DOI: 10.2337/diab.38.8.996

PMID: 2546844

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Abstract

Neuroblastoma cells were used to analyze the effect of galactose supplementation on myo-inositol metabolism, polyol accumulation, and Na+-K+ pump activity. Culturing cells in 30 mM galactose for a minimum of 1 wk led to a large accumulation of intracellular galactitol and a greater than 50% decrease in myo-inositol content. The effect of galactose on the intracellular content of galactitol and myo-inositol was concentration dependent. Extracellular myo-inositol accumulation and incorporation into phospholipid decreased by 20-30% in cells grown in 30 mM galactose. The decrease in myo-inositol accumulation is apparently due to a noncompetitive inhibition of high-affinity myo-inositol uptake. Treatment of the galactose-containing media with 0.4 mM sorbinil partially prevented the galactose-mediated decreases in myo-inositol metabolism and content. The galactitol content of the sorbinil-treated cells was significantly reduced compared with the galactitol levels in cells cultured in 30 mM galactose; however, galactitol levels remained significantly elevated over control cells. Exposing neuroblastoma cells to 30 mM galactose causes a decrease in the levels of phosphatidylinositol that is partially restored by the addition of sorbinil. The activity of the Na+-K+ pump was decreased by 20% in cells cultured in 30 mM galactose and was partially protected by sorbinil treatment. The effects of long-term galactose supplementation on myo-inositol metabolism, polyol accumulation, and Na+-K+-ATPase transport activity in cultured neuroblastoma cells are similar to the effects of high concentrations of glucose. These results provide additional evidence that the accumulation of polyol by neuroblastoma cells is partially responsible for alterations in myo-inositol metabolism and decreases in Na+-K+-ATPase transport activity.

Cell Line

Neuroblastoma - analysis

Polymers - analysis

Aldehyde Reductase - antagonists & inhibitors

Galactose - pharmacology

Inositol - metabolism

Galactose - analysis

Tumor Cells, Cultured - metabolism

Glucose - pharmacology

Imidazoles - pharmacology

Imidazolidines

Potassium Channels - metabolism

Tumor Cells, Cultured - pathology

Inositol - analysis

Sodium-Potassium-Exchanging ATPase - metabolism

Animals

Sodium Channels - metabolism

Phosphatidylinositols - metabolism

Mice

Neuroblastoma - metabolism

Glucose - analysis

Tumor Cells, Cultured - analysis

Neuroblastoma - pathology

Polymers - metabolism

Details

Title: Subtitle: Effect of galactose and glucose levels and sorbinil treatment on myo-inositol metabolism and Na+-K+ pump activity in cultured neuroblastoma cells
Creators: Mark A Yorek - Veterans Administration Medical Center, Iowa City, IA 52240
Joyce A Dunlap
Ellen M Leeney
Resource Type: Journal article
Publication Details: Diabetes (New York, N.Y.), Vol.38(8), pp.996-1004
DOI: 10.2337/diab.38.8.996
PMID: 2546844
ISSN: 0012-1797
eISSN: 1939-327X
Grant note: AM-25295 / NIADDK NIH HHS NS-23785 / NINDS NIH HHS
Language: English
Date published: 08/1989
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094662602771

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