Skip to main content
SpringerLink
Log in

Erythrocyte sodium-lithium countertransport, adenosine triphosphatase activity and sodium-potassium fluxes in insulin-dependent diabetes

  • Originals
  • Published:
International Journal of Clinical and Laboratory Research

Summary

Increased erythrocyte sodium-lithium countertransport activity has been implicated in the pathogenesis of diabetic nephropathy. However, its relationship to other cation membrane transport systems in incipient nephropathy is not yet clear. The present study was thus performed to: (1) explore associations between sodium-lithium countertransport and changes in the activity of other cation transport pathways and (2) to compare the sodium transport activities with clinical characteristics of insulin-dependent diabetic patients with and without evidence of incipient diabetic nephropathy. We measured erythrocyte sodium-lithium countertransport, passive sodium/ potassium flux (at 1°C), adenine nucleotide content in intact erythrocytes and sodium/potassium-, magnesium-and calciumdependent ATPase activity in erythrocyte membrane preparations from 34 insulin-dependent diabetic patients without microalbuminuria, 8 diabetic patients with microalbuminuria, and 8 age-matched healthy control subjects. Sodium-lithium countertransport was elevated in diabetic patients with normo- and microalbuminuria compared with control subjects [268±99 and 299(277–465), respectively, vs. 166±65 μmol/(l cells×h)] and was positively correlated (r=0.36,P<0.05) with the albumin excretion rate. However, the activity of erythrocyte membrane ATPases was significantly decreased compared with control subjects. The ATP and ADP content was found to be significantly higher (P<0.001) in erythrocytes from diabetic patients compared with control subjects (1,196±276 vs. 833±253 μmol/l cells and 353±97 vs. 255±64 μmol/l cells, respectively). The extent of erythrocyte potassium leakage correlated with hemoglobin A1c (r=0.39,P<0.05). These results demonstrate that changes in the activity of membrane cation transport, occurring in early nephropathy, are not confined to sodium-lithium countertransport, but involve various pathways, thus reflecting underlying membrane alterations which are at least partially influenced by the diabetic milieu.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

    Article  PubMed  CAS  Google Scholar 

  2. Rutherford PA, Thomas TH, Wilkinson R. Erythrocyte sodiumlithium countertransport: clinically useful, pathophysiologically instructive or just phenomenology? Clin Sci 1992; 82: 341.

    PubMed  CAS  Google Scholar 

  3. Rutherford PA, Thomas TH, Carr SJ, Taylor R, Wilkinson R. Kinetics of sodium-lithium countertransport activity in patients with uncomplicated type I diabetes. Clin Sci 1992; 82:291.

    PubMed  CAS  Google Scholar 

  4. Rabini RA, Fumelli P, Staffolani R, Mazzanti L, Pugnaloni A, Biagini G, Faloia E, Depirro R. Effects of diabetes-mellitus on structural and functional properties of erythrocyte membranes. Membr Biochem 1993; 10:71.

    Article  PubMed  CAS  Google Scholar 

  5. Solini A, DeFronzo RA. Insulin resistance, hypertension and cellular ion transport systems. Acta Diabetol 1992; 29:196.

    Article  Google Scholar 

  6. Rutherford PA, Thomas TH, Carr SJ, Taylor R, Wilkinson R. Changes in erythrocyte sodium-lithium countertransport kinetics in diabetic nephropathy. Clin Sci 1992; 82:301.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. Mangili R, Bending JJ, Scott G, Li LK, Gupta A, Viberti G. Increased sodium-lithium countertransport activity in red cells of patients with insulin-dependent diabetes and nephropathy. N Engl J Med 1988; 318:146.

    Article  PubMed  CAS  Google Scholar 

  9. Düsing R, Sorger M, Mattes L, Göbel BO, Hoffmann G, Rosskopf D, Vetter H. Platelet Na+/H+ antiport activity in patients with insulin-dependent diabetes mellitus with and without diabetic nephropathy. Clin Invest 1993; 71:119.

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  11. Postnov YV, Orlov SN. Ion transport across plasma membrane in primary hypertension. Physiol Rev 1985; 65:904.

    PubMed  CAS  Google Scholar 

  12. Huot SJ, Aronson PS. Na+−H+ exchanger and its role in essential hypertension and diabetes mellitus. Diabetes Care 1991; 14:521.

    Article  PubMed  CAS  Google Scholar 

  13. Blaustein MP. Physiological effects of endogenous ouabain: control of intracellular Ca2+ stores and cell responsiveness. Am J Physiol 1993; 264:C1367.

    PubMed  CAS  Google Scholar 

  14. Zicha J. Red cell ion transport abnormalities in experimental hypertension. Fundam Clin Pharmacol 1993; 7:129.

    Article  PubMed  CAS  Google Scholar 

  15. Morel FM. A study of passive potassium efflux from human red blood cells using ion-specific electrodes. J Membr Biol 1973; 12:69.

    Article  PubMed  CAS  Google Scholar 

  16. Gottschling HD, Jahr D, Diaz-Alonso JM, Keilacker H, Besch W, Werner S, Ziegler M. Enzymimmunoassay zur Bestimmung von Albumin im Urin. Z Med Lab Diagn 1991; 32:84.

    PubMed  CAS  Google Scholar 

  17. Elving LD, Wetzels JFM, De Pont JHHM, Berden JHM. Is increased erythrocyte sodium-lithium countertransport a useful marker for diabetic nephropathy? Kidney Int 1992; 41:862.

    PubMed  CAS  Google Scholar 

  18. Gall MA, Rossing P, Jensen JS, Funder J, Parving HH. Red cell Na+/Li+ countertransport in non-insulin-dependent diabetics with diabetic nephropathy. Kidney Int 1991; 39:135.

    PubMed  CAS  Google Scholar 

  19. Besch W, Kohnert KD, Oppermann H, Schmidt M, Klöting I, Honig A. Temperatureinfluß auf die transmembranen Ionenbewegungen der Blutzellen spontandiabetischer BB-Ratten. Nieren-und Hochdruckkrankheiten. In press.

  20. Reinila M, MacDonald E, Salem N Jr, Linnoila M, Trams EG. Standardized method for the determination of human erythrocyte membrane adenosine triphosphatases. Anal Biochem 1982; 124:19.

    Article  PubMed  CAS  Google Scholar 

  21. Bradford M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 12:248.

    Article  Google Scholar 

  22. Hurst RO. The determination of nucleotide phosphorus with a stannous chloride-hydrazine sulphate reagent. Can J Biochem 1964; 42:287.

    Article  PubMed  CAS  Google Scholar 

  23. Jensen JS, Mathiesen ER, Norgaard K, Hommel E, Borch-Johnson K, Funder J, Brahm J, Parving HH, Deckert T. Increased blood pressure and erythrocyte sodium/lithium countertransport activity are not inherited in diabetic nephropathy. Diabetologia 1990; 33:619.

    Article  PubMed  CAS  Google Scholar 

  24. Jones SL, Trevisan R, Tarig T. Sodium-lithium countertransport in microalbuminuric insulin-dependent diabetic patients. Hypertension 1990; 15:510.

    Google Scholar 

  25. Nathan DM, Siebert C, Genuth S. DCCT: design, outcomes and implications. IDF Bull [Suppl] 1994; 39:5.

    Google Scholar 

  26. Crompton CH, Balfe JW, Balfe JA, Chatzilias A, Daneman D. Sodium-lithium countertransport in adolescents with IDDM-relationship to incipient nephropathy and glycemic control. Diabetes Care 1994; 17:704.

    Article  PubMed  CAS  Google Scholar 

  27. Touyz RM, Milne FJ, Reinach SG. Platelet and erythrocyte Mg2+, Ca2+, Na+, K+ and cell membrane adenosine triphosphatase activity in essential hypertension in blacks. J Hypertens 1992; 10:571.

    Article  PubMed  CAS  Google Scholar 

  28. Harik SI, Behmand RA, Arafah BM. Chronic hyperglycemia increases the density of glucose transporters in human erythrocyte membranes. J Clin Endocrinol Metab 1991; 72:814.

    Article  PubMed  CAS  Google Scholar 

  29. Ditzel J, Andersen H, Peters ND. Increased hemoglobin A1c and 2,3-diphosphoglycerate in diabetes and their effects on red-cell oxygen-releasing capacity. Lancet 1973; II:1034.

    Article  Google Scholar 

  30. Honig A, Oppermann H, Budweg C, Goldbecher H, Freyse EJ. Demonstration of temperature dependence of Na+−K+ pump activity of human blood cells. Am J Physiol 1994; 266:S10.

    Google Scholar 

  31. Carr SJ, Mbanya JC, Thomas TH, Keavey P, Taylor R, Alberti KGMM, Wilkinson R. Increase in glomerular filtration rate in patients with insulin-dependent diabetes and elevated erythrocyte sodium-lithium countertransport. N Engl J Med 1990; 322:500.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Diabetes “Gerhardt Katsch”, Ernst Moritz Arndt University Greifswald, Greifswalder Strasse 11a, D-17495, Karlsburg, Germany

    W. Besch, H. Blücher, D. Bettin & K. -D. Kohnert

  2. Clinic of Internal Medicine, Ernst Moritz Arndt University, Greifswald, Germany

    E. Wolf

  3. Center for Diabetes and Metabolic Diseases, Clinicum Karlsburg-Greifswald, Karlsburg, Germany

    D. Michaelis

Authors
  1. W. Besch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Blücher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Bettin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Wolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. Michaelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K. -D. Kohnert
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Besch, W., Blücher, H., Bettin, D. et al. Erythrocyte sodium-lithium countertransport, adenosine triphosphatase activity and sodium-potassium fluxes in insulin-dependent diabetes. Int J Clin Lab Res 25, 104–109 (1995). https://doi.org/10.1007/BF02592366

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02592366

Key words

Search

Navigation