Effects of osmotic stress and hyperglycemia on aldose reductase gene expression in human renal proximal tubule cells.

Sorbitol levels in proximal tubule cells cultured for 96 h in the presence of 16.5 mM and 27.5 mM glucose were significantly elevated when compared to cells cultured in 5.5 mM glucose. No changes in the levels of aldose reductase activity, mRNA and immunoreactivity were observed in cells cultured for up to 168 h in media containing either 5.5 mM or 27.5 mM glucose. In contrast, cells cultured in the presence of hypertonic media (600 mosmol/kg) containing either 5.5 mM or 27.5 mM glucose contained markedly elevated aldose reductase activity, mRNA and immunoreactivity. These results demonstrate that exposure of human renal proximal tubule cells to elevated glucose for up to 168 h does not result in enhancement of aldose reductase gene expression at transcriptional, translational or post-translational levels. However, exposure to a hyperosmotic milieu causes dramatic induction of aldose reductase gene expression.