Association of 5’AMP-activated protein kinase activity with disease duration and HbA1c content in leukocytes in diabetic patients

Authors

  • L.K. Sokolova SI “V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine”, Kyiv, Ukraine
  • V.M. Pushkarev SI “V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine”, Kyiv, Ukraine
  • Yu.B. Belchina SI “V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine”, Kyiv, Ukraine
  • V.V. Pushkarev SI “V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine”, Kyiv, Ukraine
  • T.S. Vatseba SI “V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine”, Kyiv, Ukraine
  • N.D. Tronko SI “V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine”, Kyiv, Ukraine

DOI:

https://doi.org/10.22141/2224-0721.15.1.2019.158688

Keywords:

diabetes mellitus, 5’AMP-activated protein kinase, glycated hemoglobin

Abstract

Background. 5’AMP-activated protein kinase (AMPK) is an enzyme that controls the cell energy ba­lance. With energetic stress in the cell and an increase in the AMP concentration, ATP is replaced by AMP in the exchange centers, resulting in the allosteric activation of AMPK by phosphorylation of 172 threonine within alpha subunit of LKB1 complex in response to changes in cell energy or CAMKKβ, which activates intracellular Ca2+. The purpose was to study the activity of the main energy sensor of cells — AMPK in leukocytes in patients taking insulin preparations, metformin, and other hypoglycemic drugs in association with disease duration and glycated hemoglobin content. Materials and methods. The diabetic patients receiving single-drug or combined therapy with insulin and its analogues, metformin, dapagliflozin and sulfonylureas were randomized into 5 groups: the first group — with an HbA1c level close to the norm — 6.9–7.6 %; the second group — 7.6–9.0 %; the third group — > 9 %; the fourth group > 10 %; the fifth group — > 11 %. To determine the amount of phospho-AMPK (p-Thr172), ELISA kits were used. To get the calibration curve for the AMPK determination, a kidney cell culture HEK293T of the human embryonic kidney was used, which is recommended by manufacturer as a positive control. Results. It was shown that with increase of blood HbA1c, the level of AMPK activity in leukocytes gradually decreased. With increase of blood HbA1c, the level of AMPK activity in leukocytes gradually decreased. The activity of AMPK in leukocytes of patients with HbA1c > 11 % was more than 3.5-fold lower compared to the group with 6.9–7.6 % of HbA1c; AMPK activity in leukocytes in patients with disease duration of 20 years was 3-fold lower. Thus, the AMPK activity in leukocytes may be an indicator of diabetic compensation in diabetic patients. Conclusions. With increase of blood HbA1c, the level of p-AMPK in leukocytes gradually decreased. AMPK activity in leukocytes in diabetes patients with disease duration of 20 years was 3-fold lower than in patients with 10-year experience.

Downloads

Download data is not yet available.

References

Ruderman NB, Carling D, Prentki M, Cacicedo JM. AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest. 2013 Jul;123(7):2764-72. doi: 10.1172/JCI67227.

Xiao B, Sanders MJ, Underwood E, et al. Structure of mammalian AMPK and its regulation by ADP. Nature. 2011 Apr 14;472(7342):230-3. doi: 10.1038/nature09932.

Racioppi L, Means AR. Calcium/calmodulin-dependent protein kinase kinase 2: roles in signaling and pathophysiology. J Biol Chem. 2012 Sep 14;287(38):31658-65. doi: 10.1074/jbc.R112.356485.

Jeong KJ, Kim GW, Chung SH. AMP-activated protein kinase: An emerging target for ginseng. J Ginseng Res. 2014 Apr;38(2):83-8. doi: 10.1016/j.jgr.2013.11.014.

Saha AK, Xu XJ, Balon TW, Brandon A, Kraegen EW, Ruderman NB. Insulin resistance due to nutrient excess. Is it a consequence of AMPK downregulation? Cell Cycle. 2011 Oct 15;10(20):3447-51. doi: 10.4161/cc.10.20.17886.

Kojić Damjanov S, Đerić M, Eremić Kojić N. Glycated hemoglobin A1c as a modern biochemical marker of glucose regulation. Med Pregl. 2014 Sep-Oct;67(9-10):339-44.

Sokolova LK, Pushkarev VM, Belchina YB, Pushkarev VV, Tronko MD. Effect of combined treatment with insulin and metformin on 5′AMP-activated protein kinase activity in lymphocytes of diabetic patients. Dopov Nac akad nauk Ukr. 2018;(5):100-104. doi: 10.15407/dopovidi2018.05.100.

Steinberg GR, Schertzer JD. AMPK promotes macrophage fatty acid oxidative metabolism to mitigate inflammation: implications for diabetes and cardiovascular disease. Immunol Cell Biol. 2014 Apr;92(4):340-5. doi: 10.1038/icb.2014.11.

Pushkarev VM, Sokolova LK, Pushkarev VV, Tronko MD. The role of AMPK and MTOR in the development of insulin resistance and type 2 diabetes. The mechanism of metformin action (literature review). Problemi Endokrinnoi Patologii. 2016;(3):77-90. (in Ukrainian).

Galic S, Fullerton MD, Schertzer JD, et al. Hematopoietic AMPK β1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. J Clin Invest. 2011 Dec;121(12):4903-15. doi: 10.1172/JCI58577.

Hardie DG, Ross FA, Hawley SA. AMP-activated protein kinase: a target for drugs both ancient and modern. Chem Biol. 2012 Oct 26;19(10):1222-36. doi: 10.1016/j.chembiol.2012.08.019.

Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007 Jan;8(1):21-34. doi: 10.1111/j.1467-789X.2006.00270.x.

Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol. 2010 Mar 25;316(2):129-39. doi: 10.1016/j.mce.2009.08.018.

Kirchner H, Heppner KM, Tschöp MH. The role of ghrelin in the control of energy balance. Handb Exp Pharmacol. 2012;(209):161-84. doi: 10.1007/978-3-642-24716-3_7.

Downloads

Published

2019-03-26

How to Cite

Sokolova, L., Pushkarev, V., Belchina, Y., Pushkarev, V., Vatseba, T., & Tronko, N. (2019). Association of 5’AMP-activated protein kinase activity with disease duration and HbA1c content in leukocytes in diabetic patients. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), 15(1), 23–26. https://doi.org/10.22141/2224-0721.15.1.2019.158688

Issue

Section

Original Researches

Most read articles by the same author(s)

1 2 > >>