Journal article
Trans-hydroxyl group configuration on carbons 2 and 3 of glucose : responsible for acute inhibition of myo-inositol transport ?
Diabetes (New York, N.Y.), Vol.40(8), pp.1016-1023
1991
DOI: 10.2337/diab.40.8.1016
PMID: 1860553
Abstract
Cultured neuroblastoma, cerebral microvessel endothelial, and retinoblastoma cells were used to examine the mechanism of acute inhibition by D-glucose of myo-inositol uptake. Acute exposure of the cells to 30 mM D-glucose caused a significant decrease in Na+-dependent myo-inositol uptake in all three cell types. The effect of D-glucose to acutely inhibit myo-inositol uptake was dependent on the extracellular glucose concentration and was not reversed by sorbinil. 2-Deoxy-D-glucose (30 mM), 3-O-methyl-D-glucose (30 mM), and cytochalasin B (100 μM) did not acutely inhibit myo-inositol uptake. These data suggest that the hydroxyl groups on carbons 2 and 3 of D-glucose, which in a Haworth projection appear trans to each other, are important for inhibitory activity. Other monosaccharides (30 mM) having a similar 2,3-trans-diol configuration, L-glucose, D- and L-fucose, D- and L-galactose, D- and L-xylose, and D-arabinose, all to varying degrees significantly inhibited myo-inositol uptake. In all cases, the L-isomers were more potent inhibitors of myo-inositol uptake than the corresponding D-isomers. Monosaccharides (30 mM) having hydroxyl groups on carbons 2 and 3 in a cis configuration, D-mannose, L-rhamnose, D-allose, and D-ribose, did not acutely inhibit myo-inositol uptake. Replacing the hydroxyl group with a fluorine on carbons 2 or 3 of D-glucose negated its inhibitory activity of myo-inositol uptake. In contrast, replacing the hydroxyl group with a fluorine on carbon 6 of D-glucose did not block its inhibition of myo-inositol uptake. 4-Fluoro-4-deoxy-D-glucose did not block myo-inositol uptake by neuroblastoma cells but was almost as effective as D-glucose in inhibiting myo-inositol uptake by cerebral microvessel endothelial and retinoblastoma cells. These data suggest that the trans diol on carbons 2 and 3 of D-glucose is necessary for inhibition of myo-inositol transport. The hydroxyl group on carbon 4 may also be necessary for inhibitory activity; however, the stereochemical orientation of this group is not critical. myo-Inositol has four vicinal trans diols. We suggest that this configuration is important for recognition of myo-inositol by its transporter and that glucose acutely inhibits myo-inositol uptake by competing for this site.
Details
- Title: Subtitle
- Trans-hydroxyl group configuration on carbons 2 and 3 of glucose : responsible for acute inhibition of myo-inositol transport ?
- Creators
- Mark A Yorek - Univ. Iowa, diabetes endocrinology res. cent., dep. internal medicine, Iowa City IA 52246, United StatesMark R Stefani - Univ. Iowa, diabetes endocrinology res. cent., dep. internal medicine, Iowa City IA 52246, United StatesJoyce A Dunlap - Univ. Iowa, diabetes endocrinology res. cent., dep. internal medicine, Iowa City IA 52246, United StatesKee Sung Ro - Univ. Iowa, diabetes endocrinology res. cent., dep. internal medicine, Iowa City IA 52246, United StatesEric P Davidson - Univ. Iowa, diabetes endocrinology res. cent., dep. internal medicine, Iowa City IA 52246, United States
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.40(8), pp.1016-1023
- Publisher
- American Diabetes Association
- DOI
- 10.2337/diab.40.8.1016
- PMID
- 1860553
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Language
- English
- Date published
- 1991
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094762902771
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