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Platelet Na+/H+ antiport activity in patients with insulin-dependent diabetes mellitus with and without diabetic nephropathy

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Summary

The incidence of diabetic nephropathy in patients with insulin-dependent diabetes mellitus (IDDM) may depend on factors other than the quality of diabetes control. Hypertension is an additional factor associated with a high degree of renal involvement in IDDM. One abnormality consistantly observed in various tissues of patients with essential hypertension is enhanced activity of the Na+/H+ antiport. In the present study we have therefore studied platelet antiport activity in 41 healthy subjects (control), in 22 patients with untreated essential hypertension (EH), and in 35 normotensive IDDM patients (type 1). Of these patients 17 exhibited signs of diabetic nephropathy (group 1) while 18 had no evidence for renal involvement of IDDM in spite of a duration of IDDM of at least 10 years (group 2). The two IDDM patient groups were undistinguishable with respect to age, body mass index, and arterial blood pressure (group 1, 117.9±2.4/78.4±1.5 mmHg; group 2, 113.9±3.6/76.1±1.8 mmHg). Antiporter activity was determined from the rate of cell volume changes induced by propionic acid. Platelet Na+/H+ exchange activity averaged 23.43±0.43 10−3·s−1 in control subjects and was markedly elevated in EH (28.38±0.62 10−3·s−1 P<0.01). Antiport activity in group 2 patients without nephropathy averaged 24.54±0.57 10−3·s−1 and was undistinguishable from the control group. However, platelet Na+/H+ antiport activity was significantly stimulated in group 1 patients with nephropathy as compared to group 2(26.95±0.73 10−3. s−1 ; P<0.025). Our results show that renal involvement in IDDM is associated with enhanced activity of the platelet Na+/H+ antiport.

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Abbreviations

EH:

essential hypertension

HbA1c :

glycosyla-ted hemoglobin

IDDM:

insulin-dependent diabetes mellitus

References

  1. Canessa M, Adragna N, Solomon HS, Conolly TM, Tosteson DC (1980) Increased sodium-lithium countertransport in red cells of patients with essential hypertension. N Engl J Med 302:772–776

    Google Scholar 

  2. Canessa M, Morgan K, Goldszer R, Moore TJ, Spalvins A (1991) Kinetic abnormalities of the red blood cell sodium-proton exchange in hypertensive patients. Hypertension 17:340–348

    Google Scholar 

  3. Dudley CRK, Taylor DJ, Ng LL, Kemp J, Ratcliffe PJ, Radda GK, Ledingham JGG (1990) Evidence for abnormal Na+/H+ antiport activity detected by phosphorus nuclear magnetic resonance spectroscopy in exercising skeletal muscle of patients with essential hypertension. Clin Sci 79:491–497

    Google Scholar 

  4. Düsing R, Göbel BO, Hoffmann G, Siffert W, Vetter H (1990) Lymphocyte Na+/H+-exchange kinetics in essential hypertension. J Am Soc Nephrol 1:488

    Google Scholar 

  5. Feldt-Rasmussen B, Mathiesen ER, Deckert T (1986) Effect of two years of strict metabolic control on progression of incipient nephropathy in insulin-dependent diabetes. Lancet II:1300–1304

    Google Scholar 

  6. Frelin C, Vigne P, Ladoux A, Lazdunski M (1988) The regulation of the intracellular pH in cells from vertebrates. Eur J Biochem 174:3–14

    Google Scholar 

  7. Göbel BO, Hoffmann G, Ruppert M, Stumpe KO, Vetter H, Dusing R (1991) Membrane transport, sodium balance, and blood pressure regulation. Klin Wochenschr 69 [Suppl XXV]:84–89

    Google Scholar 

  8. Grinstein S, Rothstein A (1986) Mechanisms of regulation of the Na+/H+ exchanger. J Membr Biol 90:1–12

    Google Scholar 

  9. Grinstein S, Rotin D, Mason M (1989) Na+/H+ exchange and growth factor-induced cytosolic pH changes. Role in cellular proliferation. Biochim Biophys Acta 988:73–97

    Google Scholar 

  10. Grinstein S, Goetz JD, Furuya W, Rothstein A, Gelfand EW (1984) Amiloride-sensitive Na+/H+ exchange in platelets and leukocytes: detection by electronic cell sizing. Am J Physiol 247:C293-C298

    Google Scholar 

  11. Huot SJ, Aronson PS (1991) Na+-H+ exchanger and its role in essential hypertension and diabetes mellitus. Diabetes Care 14:521–535

    Google Scholar 

  12. Keil U, Döhring A, Stiebler J (1983) Community studies in the Federal Republic of Germany. In: Gross F, Strasser T (eds) Mild hypertension, recent advances. Raven, New York, pp 63–83

    Google Scholar 

  13. Krolewski AS, Warram JH, Christlieb AR, Busick EJ, Kahn CR (1985) The changing natural history of nephropathy in type 1 diabetes. Am J Med 78:785–794

    Article  CAS  PubMed  Google Scholar 

  14. Krolewski AS, Canessa M, Warram JH, Laffel LMB, Christlieb AR, Knowler WC, Rand LI (1988) Predisposition to hypertension and susceptibility to renal disease in insulin-dependent diabetes mellitus. N Engl J Med 318:140–145

    Google Scholar 

  15. Lee T-S, MacGregor LC, Fluharty SJ, King GL (1989) Differential regulation of protein kinase C and (Na,K)-adenosine triphosphatase activities by elevated glucose levels in retinal capillary endothelial cells. J Clin Invest 83:90–94

    Google Scholar 

  16. Lifton RP, Hunt SC, Williams RR, Pouyssegur J, Lalouel J-M (1991) Exclusion of the Na+-H+-antiporter as a candidate gene in human essential hypertension. Hypertension 17:8–14

    Google Scholar 

  17. Livne A, Balfe JW, Veitch R, Marquez-Julio A, Grinstein S, Rothstein A (1987) Increased platelet Na+/H+ exchange rate in essential hypertension: application of a novel test. Lancet 1:533–536

    Google Scholar 

  18. Livne A, Grinstein S, Rothstein A (1987) Characterization of Na+/H+ exchange in platelets. Thromb Haemost 58:971–977

    Google Scholar 

  19. Mangili R, Bending JJ, Scott G (1988) Increased sodium-lithium countertransport activity in red cells of patients with insulin-dependent diabetes and nephropathy. N Engl J Med 318:146–150

    Google Scholar 

  20. Ng LL, Dudley C, Bomford J, Hawley D (1989) Leucocyte intracellular pH and Na+/H+ activity in human hypertension. J Hypertens 7:471–475

    Google Scholar 

  21. Ng LL, Fennell DA, Dudley C (1990) Kinetics of the human leucocyte Na+-H+ antiport in essential hypertension. J Hypertens 8:533–537

    Google Scholar 

  22. Ng LL, Simmons D, Frighi V, Garrido MC, Bomford J (1990) Effect of protein kinase C modulators on the leucocyte Na+/H+ antiport in type 1 (insulin-dependent) diabetic subjects. Diabetologia 33:278–284

    Google Scholar 

  23. Ng LL, Simmons D, Frighi V, Garrido MC, Bomford J, Hockaday TDR (1990) Leucocyte Na+/H+ antiport activity in type 1 (insulin-dependent) diabetic patients with nephropathy. Diabetologia 33:371–377

    Google Scholar 

  24. Parving HH, Andersen AR, Smidt UM, Hommel E, Mathiesen E, Svendsen PA (1987) Effect of antihypertensive treatment on kidney function in diabetic nephropathy. BMJ 294:1443–1447

    Google Scholar 

  25. Reusch HP, Reusch R, Siffert W, Mann J, Luft FC (1991) Sodium-proton exchange in lymphocytes of patients with renal insufficiency. J Am See Nephrol 2:710

    Google Scholar 

  26. Rosskopf D, Morgenstern E, Scholz W, Osswald U, Siffert W (1991) Rapid determination of the elevated Na+/H+ exchange in platelets of patients with essential hypertension using an optical swelling assay. J Hypertens 9:231–238

    Google Scholar 

  27. Rosskopf D, Siffert G, Osswald U, Witte K, Düsing R, Akkerman JWN, Siffert W (1992) Platelet Na+/H+ exchange activity in normotensive and hypertensive subjects. Effects of enalapril therapy on antiport activity. J Hypertens 10:839–847

    Google Scholar 

  28. Salles J-P, Barthe P, Begasse F, Bouissou F, Chap H, Chamontin B (1991) Platelet sodium-proton exchange rates in young adults with a history of childhood hypertension. J Hypertens 9 [Suppl 6]:S316-S317

    Google Scholar 

  29. Salles J-P, Ser N, Fauvel J, Couvaras O, Bouissou F, Ghisolfi J, Barthe P, Chap H (1991) Platelet Na+-H+ exchange in juvenile diabetes mellitus. J Hypertens 9 [Suppl 6]:S222-S223

    Google Scholar 

  30. Sarkadi B, Parker JC (1991) Activation of ion transport pathways by changes in cell volume. Biochim Biophys Acta Rev Biomemb 1071:407–427

    Google Scholar 

  31. Schmouder RL, Weder AB (1989) Platelet sodium-proton exchange is increased in essential hypertension. J Hypertens 7:325–330

    Google Scholar 

  32. Seaquist ER, Goetz FC, Rich S, Barbosa J (1987) Concordance for nephropathy in diabetic siblings: evidence of genetic susceptibility to diabetic kidney disease. Diabetes 36 [Suppl]:105A

  33. Semplicini A, Mozzato M-G, Sama B, Nosadini R, Fioretto P, Trevisan R, Pessina AC, Crepaldi G, Dal Palu C (1989) Na/H and Li/Na exchange in red blood cells of normotensive and hypertensive patients with insulin-dependent diabetes mellitus (IDDM). Am J Hypertens 2:174–177

    Google Scholar 

  34. Semplicini A, Canessa M, Mozzato MG, Ceolotto G, Marzola M, Buzzaccarini F, Casolino P, Pessina AC (1989) Red blood cell Na+/H+ and Li+/Na+ exchange in patients with essential hypertension. Am J Hypertens 2:903–908

    Google Scholar 

  35. Strazullo P, Canessa M (1990) Kinetics of the human lymphocyte Na+/H+ exchanger. Clin Sci 79:531–536

    Google Scholar 

  36. Tamaoki T, Nomoto H, Takahashi I, Kato Y, Morimoto M, Tomita F (1986) Staurosporine, a potent inhibitor of phospholipid/Ca++ dependent protein kinase. Biochem Biophys Res Commun 135:397–402

    Google Scholar 

  37. Tokudome G, Tomonari H, Gardner JP, Aladjem M, Fine BP, Lasker N, Gutkin M, Byrd LH, Aviv A (1990) Variations in the apparent set point for activation of platelet Na+/H+ antiport. Hypertension 16:180–189

    Google Scholar 

  38. Viberti BC, Bilous RW, Mackintoch D, Bending JJ, Keen H (1983) Long term correction of hyperglycaemia and progression of renal failure in insulin-dependent diabetes. BMJ 286:598–602

    Google Scholar 

  39. Viberti GC, Keen H, Wiseman MJ (1987) Raised arterial pressure in parents of proteinuric insulin-dependent diabetics. BMJ 295:515–517

    Google Scholar 

  40. Weder AB, Schmouder RL, Torretti BA (1990) Platelet volume responses to cytoplasmic acidification in essential hypertension. J Hypertens 8:1137–1142

    Google Scholar 

  41. Weling M, Käsmayr J, Theisen K (1991) The Na+-H+ exchanger is stimulated and cell volume increased in lymphocytes from patients with essential hypertension. J Hypertens 9:519–524

    Google Scholar 

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Authors and Affiliations

  1. Medizinische Universitäts-Poliklinik Bonn, Wilhelmstrasse 35-37, W-5300, Bonn 1, FRG

    R. Düsing, M. Sorger, L. Mattes, B. O. Göbel, G. Hoffmann & H. Vetter

  2. Max-Planck-Institut für Biophysik Frankfurt/Main, FRG

    D. Rosskopf & W. Siffert

Authors
  1. R. Düsing
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  2. M. Sorger
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  3. L. Mattes
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  4. B. O. Göbel
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  5. G. Hoffmann
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  6. D. Rosskopf
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  7. H. Vetter
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  8. W. Siffert
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Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday

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Düsing, R., Sorger, M., Mattes, L. et al. Platelet Na+/H+ antiport activity in patients with insulin-dependent diabetes mellitus with and without diabetic nephropathy. Clin Investig 71, 119–125 (1993). https://doi.org/10.1007/BF00179992

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  • DOI: https://doi.org/10.1007/BF00179992

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