Intermittent high glucose enhances cell growth and collagen synthesis in cultured human tubulointerstitial cells

Aims/hypothesis. We investigated the effects of constant and intermittently increased glucose concentrations on human proximal tubule cells and cortic al fibroblasts in primary culture. Methods. Cells were grown to confluence and then exposed for 3 days to 6.1 mmol/l D-glucose (normal), 25 mmol/l D-glucose thigh), or 6.1 mmol/l altern ating with 25 mmol/l D-glucose on a daily basis. Results. In proximal tubular cells, exposure to high glucose caused an 11% increase in thymidine uptake (p < 0.05), a 230% increase in secretion of tr ansforming growth factor beta 1 (TGF-beta 1; p < 0.05) and a 393% increase in platelet derived growth factor. Intermittent exposure to high glucose ca used thymidine uptake to further increase by 42% (p < 0.01) and TGF-beta 1 secretion by 352% (p < 0.01) but no additional increase in platelet-derived growth factor secretion was observed. Cellular protein content increased b y 27% (p < 0.05) and collagen synthesis by 29% (p < 0.05), changes that wer e not observed in cells constantly exposed to high glucose. In cortical fib roblasts constant exposure to high glucose caused a 35% increase in thymidi ne uptake (p < 0.01). Intermittently high glucose increased thymidine incor poration a further 58% (p < 0.001), collagen synthesis by 65% (p < 0.01) an d insulin-like growth factor binding protein 3 secretion by 216% (p < 0.01) . Conclusion/interpretation. In cultured human tubulointerstitial cells, incr eased glucose concentrations change cell growth, collagen synthesis and cyt okine secretion. These effects are enhanced following intermittent exposure to high glucose, indicating that short lived excursions in glycaemic contr ol have important pathological effects on the human tubulointerstitium.