ENHANCED GROWTH AND NA+ H+ ANTIPORT ACTIVITY RESPONSE TO SERUM IN CULTURED FIBROBLASTS OF DIABETIC-PATIENTS WITH NEPHROPATHY/

To explore whether elevated red blood cell sodium-lithium countertrans port in type 1 (insulin-dependent) diabetic patients with nephropathy is related to the physiological Na+/H+ antiport activity, we measured the activity of this antiport in serially passaged cultured skin fibro blasts from insulin-dependent diabetic patients with and without nephr opathy and from non-diabetic controls. Na+/H+ antiport activity (measu red as the rate of amiloride-sensitive Na+ influx) was significantly e levated in patients with nephropathy compared with patients without ne phropathy and normal controls (13.35 +/- 3.8 vs 8.54 +/- 2.0 vs 7.33 /- 2.3 nmol Na+/mg protein per min; P < 0.006 and P < 0.001 respective ly). This raised activity in patients with nephropathy was due to an i ncreased V(max) for extracellular Na+. K(m) values were similar in the three groups. Amiloride-sensitive Na+ influx was also higher in cells under baseline conditions and after serum stimulation from patients w ith nephropathy. Intracellular pH values were significantly higher, bo th during active proliferation and after 10 min of exposure to serum, in cells from patients with nephropathy compared with patients without nephropathy and normal controls. Serum-stimulated incorporation of [H -3]thymidine into DNA was greater in patients with nephropathy than in the other two groups. These data in cultured fibroblasts suggest that intrinsic abnormalities in cell function, independently of the metabo lic disturbances of diabetes, are a feature of diabetic patients who d evelop nephropathy.