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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Oct 15;90(20):9712–9716. doi: 10.1073/pnas.90.20.9712

Ambient glucose and aldose reductase-induced myo-inositol depletion modulate basal and carbachol-stimulated inositol phospholipid metabolism and diacylglycerol accumulation in human retinal pigment epithelial cells in culture.

T P Thomas 1, E L Feldman 1, J Nakamura 1, K Kato 1, M Lien 1, M J Stevens 1, D A Greene 1
PMCID: PMC47640  PMID: 8415767

Abstract

Physiological hyperglycemia has been speculated to alter phosphoinositide (PPI; inositol phospholipid) signal transduction in cells prone to diabetic complications by two separate mass-action mechanisms with antiparallel putative effects on diacylglycerol (DAG): (i) sorbitol-induced depletion of myo-inositol leads to diminished PPI synthesis and turnover and DAG release, and (ii) elevated glucose-derived DAG precursors enhance de novo DAG synthesis. Because the first mechanism is mediated by aldose reductase (AR2), which converts glucose to sorbitol, the effects of glucose on basal and stimulated PPI signaling were explored in lines of cultured human retinal pigment epithelial cells differing widely in their basal AR2 gene expression and enzymatic activity. The results suggest that the effects of glucose on PPI signaling vary inversely with the level of AR2 activity and parallel the extent of AR2-induced myo-inositol depletion.

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Selected References

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