Purine nucleotides and their metabolites in patients with type 1 and 2 diabetes mellitus


We measured the erythrocyte levels of principal nucleotides (ATP, ADP, AMP, GTP, GDP, GMP, IMP), nucleosides (Ado, Guo, Ino) and Hyp with HPLC. Purine concentrations were determined in the erythrocytes of 36 type 1 and 40 type 2 diabetic patients. The increased dephosphorylation of adenine and guanine nucleotides, indicated by increased Ado, Ino, Guo and Hyp concentrations as the products of purine nucleotide degradation, suggests serious energy metabolism disruptions in diabetes. An increase in AMP, GMP, IMP concentrations, as well as a decrease in AEC and GEC values, points to significant alterations in erythrocyte purine nucleotide concentration.

Share and Cite:

Dudzinska, W. (2014) Purine nucleotides and their metabolites in patients with type 1 and 2 diabetes mellitus. Journal of Biomedical Science and Engineering, 7, 38-44. doi: 10.4236/jbise.2014.71006.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Dudzinska, W., Hlynczak, A.J., Skotnicka, E., et al. (2006) The purine metabolism of human erythrocytes. Biochemistry (Moscow), 71, 467-475. http://dx.doi.org/10.1134/S0006297906050014
[2] Baldini, P., Incerpi, S., Pascale, E., et al. (1986) Insulin effects on human red blood cells. Molecular and Cellular Endocrinology, 46, 93-102. http://dx.doi.org/10.1016/0303-7207(86)90087-0
[3] Jamal, Z. and Saggerson, E.D. (1987) Enzymes involved in Ado metabolism in rat white and brown adipocytes. Effects of streptozotocin-diabetes, hypothyroidism, age and sex differences. Biochemical Journal, 245, 881-886.
[4] Jenkins, R.L., Daniel, M.C., Digernes, S., et al. (1988) Adenine nucleotide metabolism in hearts of diabetic rats. Comparision to diaphragm, liver and kidney. Diabetes, 37, 629-636. http://dx.doi.org/10.2337/diab.37.5.629
[5] Hoshino, T., Yamada, K. and Masuoka, K. (1994) Elevated adenosine deaminase activity in the serum of patients with diabetes mellitus. Diabetes Research and Clinical Practice, 25, 97-102. http://dx.doi.org/10.1016/0168-8227(94)90034-5
[6] Sakowicz, M. and Pawelczyk, T. (2002) Insulin restores expression of adenosine kinase in streptozotocin-induced diabetes mellitus rats. Molecular and Cellular Bio-chemistry, 236, 163-171. http://dx.doi.org/10.1023/A:1016163517896
[7] Donatelli, M., Russo, V. and Bucalo, M.L. (1990) Increase in red cell lactate concentration and its reduction by isologus plasma in NIDDM subjects. Diabetes Research, 15, 33-35.
[8] Donatelli, M., Russo, V., Bucalo, M.L., et al. (1989) Erythrocyte glucose, ATP, lactate concentration and their modifications induced by isologus plasma in non-insulin-dependent diabetes mellitus. Diabetes Research, 16, 121-125.
[9] Suhail, M. and Rizvi, S. (1989) Effectt of type I diabetes mellitus on key glicolytic enzymes of red blood cells. Acta Diabetologica Latina, 26, 315-320. http://dx.doi.org/10.1007/BF02624643
[10] Bettini, D., Kloting, I. and Kohner, K.D. (1996) Alterations in erythrocyte plasma membrane ATPase activity and adenine nucleotide content in spontaneously diabetic subline of the Chinese hamster. Hormone and Metabolic Research, 28, 1-6. http://dx.doi.org/10.1055/s-2007-979119
[11] Rabini, R.A., Fumelli, P. and Staffolani, R. (1996) Effects of diabetes mellitus on structural and functional properties of erythocyte membranes. Molecular Membrane Biology, 10, 71-79. http://dx.doi.org/10.3109/09687689309150254
[12] Rabini, R.A., Petruzzi, E., Staffolani, R., et al. (1997) Diabetes mellitus and subjects’ ageing: A study on the ATP content and ATP-related enzyme activites in human erythrocytes. European Journal Clinical Investigation, 27, 327-332. http://dx.doi.org/10.1046/j.1365-2362.1997.1130652.x
[13] Garner, M.H. (1996) Changes in Na, K-ATPase concentration and Na, K-ATPase—Dependent adenosine triphosphate turnover in human erythrocytes in diabetes. Metabolism, 45, 927-934. http://dx.doi.org/10.1016/S0026-0495(96)90257-7
[14] Smolenski, R.T., Lachno, D.R., Ledingham, S.J.M., et al. (1990) Determination of sixteen nucleotides, nucleosides and bases using high-performance liquid chromatography and its application to the study of purine metabolism in heart for transplantation. Journal of Chromatography, 527, 414-420.
[15] Dudzinska, W. and Hlynczak, A.J. (2004) Purine nucleotides and their metabolites in erythrocytes of streptozotocin diabetic rats. Diabetes Metabolism, 30, 557-567. http://dx.doi.org/10.1016/S1262-3636(07)70155-6
[16] Olah, M.E. and Stiles, G.L. (2000) The role of receptor structure in determining adenosine receptor activity. Pharmacology & Therapeu, 85, 55-75. http://dx.doi.org/10.1016/S0163-7258(99)00051-0
[17] Stiles, G.L. (1992) Adenosine receptors. Journal of Biological Chemistry, 267, 6451-6454.
[18] Cassar, M., Jones, M.G. and Szatkowski, M. (1998) Reduced adenosine uptake accelerates ischaemic block of population spicas in hippocampal slices from streptozotocin-treated diabetic rats. European Journal of Neuroscience, 10, 239-245. http://dx.doi.org/10.1046/j.1460-9568.1998.00035.x
[19] Pawelczyk, T., Sakowicz, M., Szczepanska-Konkel, M., et al. (2000) Decreased expression of adenosine kinase in streptozotocin-induced diabetes mellitus rats. Archives of Biochemistry and Biophysics, 375, 1-6. http://dx.doi.org/10.1006/abbi.1999.1548
[20] Pawelczyk, T., Podgorska, M. and Sakowicz, M. (2003) The effect of insulin on expression level of nucleoside transporters in diabetic rats. Molecular Pharmacology, 63, 81-88. http://dx.doi.org/10.1124/mol.63.1.81
[21] Sobrevia, L., Jarris, S.M. and Yudibevich, D.L. (1994) Adenosine transport in culture human umbilical vein endothelial cells is reduced in diabetes. Cell Physiology, 36, 39-47.
[22] Klabunde, R.E. (1983) Effects of dipyridamole on postischemic vasodilation and extracellular adenosine. American Journal of Physiology, 244, 273-278.
[23] Bontemps, F., Van den Berghe, G. and Hers, G. (1986) Pathways of adenine nucleotide catabolism in erythrocytes. The Journal of Clincal Investigation, 77, 824- 830. http://dx.doi.org/10.1172/JCI112379
[24] Komarova, S., Mosharov, E.V., Vitvitskii, V., et al. (1999) Adenine nucleotide synthesis in human erythrocytes depends on the mode of supplementation of cell suspension with adenosine. Blood Cells, Molecules & Diseases, 25, 170-179. http://dx.doi.org/10.1006/bcmd.1999.0243
[25] Ataullakhanov, F.I., Vitvitskii, V.M. and Komarova, S.V. (1996) Energy dependent processes and adenylate metabolism in human erythrocytes. Biochemistry (Moscow), 61, 197-203.
[26] Kim, H.D. (1990) Is adenosine a second metabolic substrate for human red blood cells. Biochimica et Biophysica Acta, 1036, 113-120. http://dx.doi.org/10.1016/0304-4165(90)90022-O
[27] Namiot, Z., Baranczuk, E. and Wojcik, B. (1993) Adenosine deaminase activity in various parts of the gastrointestinal tract of streptozotocin treated rats. Pharmazie, 48, 950-954.
[28] Rutkiewicz, J. and Górski, J. (1990) On the role of insulin in regulation of adenosine deaminase activity in rat tissue. FEBS Letter, 271, 79-80. http://dx.doi.org/10.1016/0014-5793(90)80376-T
[29] Mabley, J.G., Rabinovitch, A., Suarez-Pinzon, W., et al. (2003) Inosine protects against the development of diabetes in multiple-low-dose streptozotocin and nonobese diabetic mouse models of type 1 diabetes. Molecular Medicine, 9, 96-104. http://dx.doi.org/10.2119/2003-00016.Mabley

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.