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 cortical fibroblasts in primary culture. Methods. Cells were grown to confluence and then exposed for 4 days to 6.1 mmol/l d-glucose (normal), 25 mmol/l d-glucose (high), or 6.1 mmol/l alternating 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 transforming growth factor beta 1 (TGF-β1; p < 0.05) and a 393 % increase in platelet derived growth factor. Intermittent exposure to high glucose caused thymidine uptake to further increase by 42 % (p < 0.01) and TGF-β1 secretion by 352 % (p < 0.01) but no additional increase in platelet-derived growth factor secretion was observed. Cellular protein content increased by 27 % (p < 0.05) and collagen synthesis by 29 % (p < 0.05), changes that were not observed in cells constantly exposed to high glucose. In cortical fibroblasts constant exposure to high glucose caused a 35 % increase in thymidine uptake (p < 0.01). Intermittently high glucose increased thymidine incorporation a further 58 % (p < 0.001), collagen synthesis by 65 % (p < 0.01) and insulin-like growth factor binding protein 3 secretion by 216 % (p < 0.01). Conclusion/interpretation. In cultured human tubulointerstitial cells, increased glucose concentrations change cell growth, collagen synthesis and cytokine secretion. These effects are enhanced following intermittent exposure to high glucose, indicating that short lived excursions in glycaemic control have important pathological effects on the human tubulointerstitium. [Diabetologia (1999) 42: 1113–1119]