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Enhanced growth and Na+/H+ antiport activity response to serum in cultured fibroblasts of diabetic patients with nephropathy

Abstract

To explore whether elevated red blood cell sodium-lithium countertransport 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 fibroblasts from insulin-dependent diabetic patients with and without nephropathy and from non-diabetic controls. Na+/H+ antiport activity (measured as the rate of amiloride-sensitive Na+ influx) was significantly elevated in patients with nephropathy compared with patients without nephropathy 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 andP<0.001 respectively). This raised activity in patients with nephropathy was due to an increasedV 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 with nephropathy. Intracellular pH values were significantly higher, both 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 [3H]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 metabolic disturbances of diabetes, are a feature of diabetic patients who develop nephropathy.

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Correspondence to R. Trevisan.

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Trevisan, R., Yip, J., Li, L.K. et al. Enhanced growth and Na+/H+ antiport activity response to serum in cultured fibroblasts of diabetic patients with nephropathy. Acta Diabetol 29, 178–181 (1992). https://doi.org/10.1007/BF00573484

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Key words

  • Cell proliferation
  • Diabetic nephropathy
  • Intracellular pH
  • Skin fibroblasts
  • Sodium-hydrogen exchange