High glucose induces the activity and expression of Na+/H+ exchange in glomerular mesangial cells

Changes in activity or expression of transporters may account for alteratio ns in cell behavior ill diabetes. We sought to ascertain if mesangial cells (MC) gr own in different glucose concentrations exhibit changes in activit y and expression of acid-extruding transporters, the Na+/H+ and Na+-depende nt Cl-/ HCO3- exchanger. pH(i) was determined by the use of the fluorescent pH-sensitive dye BCECF. In MCs grown in 5 mM glucose (control), the Na+/H exchanger was responsible for 31.8 +/- 5.1% of steady-state pH(i), whereas Na+ -dependent Cl-/ HCO, contributed 62.9 +/- 4.0% (n = 11). In MCs grown in high glucose for 2 wk, Na+/H+ exchange contribution to acid-extrusion in creased as follows: 42.3 +/- 4.6% [n = 8, 10 mM, not significant (NS)], 51. 1 +/- 5.1%% (n = 8, 20 mM, P < 0.01), and 64.8 +/- 5.5% (n = 7, 30 mM, P < 0.001). The Nac-dependent Cl-/HCO3- exchanger contributed less [47.0 +/- 4. 6, 38.6 +/- 5.8, and 21.1 +/- 3.8%, for 10, 20, and 30 mM glucose, respecti vely (n > 7)]. We sought to ascertain if the magnitude of the acute stimula ted response to ANG II by the Na+/H+ and Na+-dependent Cl-/HCO3- exchanger is changed. Na+/H+ exchanger (1.89-fold increase in 30 vs. 5 mM, P < 0.002) , but not Na+-dependent Cl-/HCO3- exchange (0.17-fold, NS), exhibited an en hanced response to ANG II (1 mu M). Na+/H+ exchange (NHE1) expression was s ignificantly different (1.72-fold) after prolonged exposure to high glucose . These results suggest that the Na+/H+ exchanger, but not Na+-dependent Cl -/HCO3- exchanger, may play an early role in the response to hyperglycemia in the diabetic state.