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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Seaquist ER, Goetz FC, Rich S, Barbosa J, Familial clustering of diabetic kidney disease. N Engl J Med 320:1161–1165, 1989
Mangili R, Bending JJ, Scott G, Li LK, Gupta A, Vibert GC, Increased sodium-lithium countertransport activity in red cells of patients with insulin-dependent diabetes and nephropathy. N Engl J Med 318:146–150, 1988
Krolewski AS, Canessa M, Warram JH, Laffel LMB, Christlieb AR, Knowler WC, Rand LI, Predisposition to hypertension and susceptibility to renal disease in insulin-dependent diabetes mellitus. N Engl J Med 318:140–145, 1988
Jones SL, Trevisan R, Tariq T, Semplicini A, Mattock M, Walker JD, Nosadini R, Viberti GC, Sodium-lithium countertransport in microalbuminuric insulin-dependent diabetic patients. Hypertension 15:570–575, 1990
Canessa M, Adragna N, Salomon HS, Connolly TM, Tosteson DC, Increased sodium-lithium countertransport activity in red cells of patients with essential hypertension. N Engl J Med 302:772–776, 1980
Walker JD, Tariq T, Viberti GC, Sodium-lithium countertransport activity in red cells of patients with insulin-dependent diabetes and nephropathy and their parents. BMJ 301:635–638, 1990
Osterby R, Gundersen HJG, Glomerular size and structure in diabetes mellitus. I. Early abnormalities. Diabetologia 11:225–229, 1975
Trevisan R, Nosadini R, Fioretto P, Semplicini A, Donadon V, Doria A, Nicolosi G, Zanuttini D, Cipollina MR, Lusiani L, Avogaro A, Crepaldi G, Viberti GC, Clustering of risk factors in hypertensive insulin-dependent diabetics with high sodium-lithium countertransport. Kidney Int 1992 (in press)
Canessa ML, Morgan K, Semplicini A, Genetic differences in lithium-sodium exchange and regulation of the sodium-hydrogen exchange in essential hypertension. J Cardiovasc Pharmacol 12 [Suppl 3]:S92-S98, 1988
Mahnensmith RL, Aronson PS, The plasma membrane sodium-hydrogen exchanger and its role in physiological and pathophysiological processes. Circ Res 56:773–788, 1985
Semplicini A, Mozzato MG, Samà B, Nosadini R, Fioretto P, Trevisan R, Pessina A, Crepaldi G, Dal Palù D, Sodium-hydrogen and lithium-sodium exchange in red cells of normotensive and hypertensive patients with insulin-dependent diabetes mellitus. Am J Hypertens 2:174–177, 1989
Ng LL, Simmons D, Frighi V, Garrido MC, Bomford J, Effect of protein kinase C modulators on the leucocyte Na+/H+ antiport in type 1 (insulin-dependent) diabetic subjects with albuminuria. Diabetologia 33:278–284, 1990
Paris S, Pouyssegur J, Growth factors activate the Na/H antiporter in quiescent fibroblast by increasing its affinity for intracellular H+. J Biol Chem 259:10989–10994, 1984
L'Allemain G, Paris S, Pouyssegur J, Growth action and intracellular pH regulation in fibroblasts. J Biol Chem 259:5809–5815, 1984
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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
- Cell proliferation
- Diabetic nephropathy
- Intracellular pH
- Skin fibroblasts
- Sodium-hydrogen exchange