Share This Article:

Adenylate kinase locus 1 genetic polymorphism and type 2 diabetes

Abstract Full-Text HTML Download Download as PDF (Size:137KB) PP. 77-81
DOI: 10.4236/health.2011.32014    3,719 Downloads   6,952 Views   Citations


AK1 catalyzes the reversible reaction ATP+AMP ? 2ADP thus contributing to the regulation of relative concentration of these important nu-cleotides. Intracellular ATP is a storage of en-ergy for cellular processes, moreover extracel-lular ATP together with ADP, AMP and adeno-sine are critical signalling molecule for sending messages to nearby cells acting on P1 and P2 receptors. AK1 shows a genetic polymorphism and recently our group has shown that the cor-relation between blood glucose and glycated haemoglobin in T2D is dependent on AK1 phe-notype. In the present paper we have carried further studies on the relationship between AK1 phenotypes and T2D. Possible interactions with ABO blood groups and ACP1 polymorphism have also been investigated. We have re-ex-amined the data on 280 subjects with type 2 diabetes from the White population of Penne (Central Italy). 384 consecutive healthy new-borns from the same population have been also studied. A three way contingency table analysis was carried out according to Sokal and Rohlf and other statistical analyses by SPSS pro-grams. T2D patients with AK12-1 phenotype have higher values of blood glucose level and glycated haemoglobin and an increased ten-dency to dyslipidemia and retinopathy. In addi-tion there is an interaction of AK1 with ABO blood groups and with ACP1 polymorphism. The different activity between AK1 phenotypes could influence the relative concentration of ATP, ADP, AMP and adenosine with important effects on metabolic activity thus explaining the associa-tion of AK1 with clinical manifestation of T2D.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Gloria-Bottini, F. , Antonacci, E. , Neri, A. , Magrini, A. and Bottini, E. (2011) Adenylate kinase locus 1 genetic polymorphism and type 2 diabetes. Health, 3, 77-81. doi: 10.4236/health.2011.32014.


[1] Khakh, B.S. and Burnstock, G. (2009) The double life of ATP. Scientific American, 301, 84-90. doi:10.1038/scientificamerican1209-84
[2] Dzeja, P. and Terzic, A. (2009) Adenylate kinase and AMP signaling networks: Metabolic monitoring, signal communication and body energy sensing. International Journal of Molecular Sciences, 10, 1729-1772. doi:10.3390/ijms10041729
[3] Matsuura, S., Igarashi, M., Tanizawa, Y., Yamada, M., Kishi, F., Kajii, T., Fujii, H., Miwa, S., Sakurai, M. and Nakazawa, A. (1989) Human adenylate kinase deficiency associated with hemolytic anemia. A single base substitution affecting solubility and catalytic activity of the cytosolic adenylate kinase. Journal of Biological Chemistry, 264, 10148-10155.
[4] Gloria-Bottini, F., Antonacci, E., Cozzoli, E., De Acetis, C. and Bottini, E. (2010) The effect of genetic variability on the correlation between blood glucose and glycated hemoglobin levels. Metabolism, 60, 250-255. doi:10.1016/j.metabol.2010.01.003
[5] Weitkamp, L.R., Sing, C.F., Shreffler, D.C. and Guttormsen, S.A. (1969) The genetic linkage relations of adenylate kinase: Further data on the ABO-AK linkage group. American Journal of Human Genetics, 21, 600- 605.
[6] Bottini, N., Gloria-Bottini, F., Borgiani, P., Antonacci, E., Lucarelli, P. and Bottini, E. (2004) Type 2 diabetes and the genetics of signal transduction: a study of interaction between adenosine deaminase and acid phosphatase locus 1 polymorphisms. Metabolism, 53, 995-1001. doi:10.1016/j.metabol.2004.03.006
[7] Fildes, R.A. and Harris, H. (1966) Genetically determined variation of adenylate kinase in man. Nature, 209, 261-263. doi:10.1038/209261a0
[8] Spencer, N., Hopkinson, D.A. and Harris, H. (1964) Quantitative differences and gene dosage in the human red cell acid phosphatase polymorphism. Nature, 201, 299- 300. doi:10.1038/201299a0
[9] SPSS/PC+ Version 5.0 (1992) Chicago: SPSS Inc.
[10] Sokal, R.R. and Rohlf, J.F. (1981) Biometry, WH Freeman, New York.
[11] Petit, P., Lajoix, A.D. and Gross, R. (2009) P2 purinergic signalling in the pancreatic beta-cell: Control of insulin secretion and pharmacology. European Journal of Pharmaceutical Sciences, 37, 67-75. doi:10.1016/j.ejps.2009.01.007
[12] Solini, A., Chiozzi, P., Morelli, A., Passaro, A., Fellin, R. and Di Virgilio, F. (2003) Defective P2Y purinergic receptor function: A possible novel mechanism for impaired glucose transport. Journal of Cellular Physiology, 197, 435-444. doi:10.1002/jcp.10379
[13] Misra, P. and Chakrabarti, R. (2007) The role of AMP kinase in diabetes. Indian Journal of Medical Research, 125, 389-398.
[14] Miranda, N., Tovar, A.R., Palacios, B. and Torres, N. (2007) AMPK as a cellular energy sensor and its function in the organism. Revista de Investigacion Clinica, 59, 458- 469.
[15] Remedi, M.S. and Koster, J.C. (2010) K(ATP) channelopathies in the pancreas. Pflugers Archiv, 460, 307-320.
[16] Wasada, T. (2002) Adenosine triphosphate-sensitive potassium (K(ATP)) channel activity is coupled with insulin resistance in obesity and type 2 diabetes mellitus. Internal Medicine, 41, 84-90.
[17] Chistiakov, D.A., Potapov, V.A., Khodirev, D.C., Shamkhalova, M.S., Shestakova, M.V. and Nosikov, V.V. (2009) Genetic variations in the pancreatic ATP-sensitive potassium channel, beta-cell dysfunction, and susceptibility to type 2 diabetes. Acta Diabetol, 46, 43-49.

comments powered by Disqus

Copyright © 2018 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.