EFFECT OF COMBINED TREATMENT WITH INSULIN AND OTHER HYPOGLYCEMIC DRUGS ON 5'AMP-ACTIVATED PROTEIN KINASE ACTIVITY IN LEUCOCYTES OF PATIENTS WITH DIABETES MELLITUS
DOI:
https://doi.org/10.21856/j-PEP.2019.3.10Keywords:
AMRK, leukocytes, type 2 diabetes, metformin, insulin, gliclazide MR, dapagliflozinAbstract
The composition of leukocytes includes monocytes/macrophages and lymphocytes - cells, inflammation and infiltration of which is an important event in the pathogenesis of diabetes and related complications. The enzyme immunoassay method determined in leukocytes the level of threonine 172 phosphorylation (activation) of 5’adenosine monophosphate-activated protein kinase (AMPK), which controls the cell energy balance, in the combined treatment of patients with with insulin, metformin, gliklazidy MR and g, and the rats of heart and glyclaside MR and chromploidine, and ga; The level of threonine 172 phosphorylation (activation) of 5'-adenosine monophosphate-activated protein kinase (AMPK), controlling the energy balance of the cell, at combination treatment of patients with type 2 diabetes (T2D) with insulin, metformin, gliclazide and dapagliflozin was determined in blood cells by enzyme immunoassay. It has been shown that metformin drugs increase the activity of AMPK in the blood cells of patients with T2D more than 3-6 times compared with patients before treatment. Insulin and its analogue completely suppress AMPK activity, induced by metformin in the leucocytes of patients with T2D, which may indicate a decrease in the therapeutic effect of metformin. Gliclazide MR increases the activity of AMPK in blood mononuclear cells. In the presence of both metformin and gliclazide, the level of AMPK phosphorylation is reduced. The mechanism of activation of AMPK by gliclazide probably related to the effect of the latter on Ерас2А. Dapagliflozin increases the activity of AMPK and enhances the effect of metformin in the leucocytes of patients with T2D. AMPK activity in blood cells can serve as one of the indicators of the effectiveness of the hypoglycemic drugs action. The mechanisms of drug interaction and the consequences of their antagonism are discussed.
References
Ruderman NB, Carling D, Prentki M, Cacicedo JM. J Clin Invest 2013; 123(7): 2764-2772. https://doi.org/10.1172/JCI67227.
Xiao B, Sanders MJ, Underwood E, et al. Nature 2011; 472(7342): 230-233. https://doi.org/10.1038/nature09932.
Racioppi L, Means AR. J Biol Chem 2012; 287(38): 31658-31665. https://doi.org/10.1074/jbc.R112.356485.
Jeong KJ, Kim GW, Chung SH. J Ginseng Res 2014;38: 83-88. https://doi.org/10.1016/j.jgr.2013.11.014.
An H, He L. J Endocrinol 2016; 228(3): R97-R106. https://doi.org/10.1530/JOE-15-0447.
Diabetes Care 2 018; 41(1): S1-S2. https://doi.org/10.2337/dc18-Sint01.
Hung AM, Roumie CL, Greevy RA, et al. Clin J Am Soc Nephrol 2016; 11(12): 2177-2185. https://doi.org/10.7326/0003-4819-157-9-201211060-00003.
Roumie CL, Greevy RA, Grijalva CG, et al. JAMA 2014; 311(22): 2288-2296. https://doi.org/10.1001/jama.2014.4312.
Roumie CL, Min JY, D’Agostino McGowan L, et al. J Am Heart Assoc 2017; 6(4): e005379. https://doi.org/10.1161/JAHA.116.005379.
Molinuevo MS, Schurman L, McCarthy AD, et al. J Bone Miner Res 2010;25(2): 211-221. https://doi.org/10.1359/jbmr.090732.
Meng S, Cao J, He Q, et al. J Biol Chem 2015; 290: 3793-3802. https://doi.org/10.1074/jbc.M114.604421.
Yang X, Xu Z, Zhang C, et al. Biochim Biophys Acta 2017; 1863(8): 1984-1990. https://doi.org/10.1016/j.bbadis.2016.09.019.
Valentine RJ, Coughlan KA, Ruderman NB, Saha AK. Arch Biochem Biophys 2014; 562: 62-69. https://doi.org/10.1016/j.abb.2014.08.013.
Omar B, Zmuda-Trzebiatowska E, Manganiello V, et al. Cell Signal 2009; 21(5): 760-766. https://doi.org/10.1016/j.cellsig.2009.01.015.
Kido K, Yokokawa T, Ato S, et al. Am J Physiol Regul Integr Comp Physiol 2017; 313(2): R110-R119. https://doi.org/10.1152/ajpregu.00063.2017.
Hemmingsen B, Schroll JB, Wetterslev J, et al. CMAJ Open 2014; 2: E162-E175. https://doi.org/10.9778/cmajo.20130073.
ADVANCE Collaborative Group, Patel A, MacMahon S, et al. N Engl J Med 2008; 358: 2560-2572. https://doi.org/10.1056/NEJMoa0802987.
Hirst JA, Farmer AJ, Dyar A, et al. Diabetologia 2013; 56: 973-984. https://doi.org/10.1007/s00125-013-2856-6.
Han YE, Lim A, Park SH, et al. Exp Mol Med 2015; 47: e190. https://doi.org/10.1038/emm.2015.72.
Wu Y, Shyng SL, Chen PC. J Biol Chem 2015; 290(50): 29676-29690. https://doi.org/10.1074/jbc.M115.670877.
Abraham MA, Yue JT, LaPierre MP, et al. Mol Metab 2013; 3(2): 202-208. https://doi.org/10.1016/j.molmet.2013.11.007.
Seino S. Diabetologia 2012; 55: 2096-2108. https://doi.org/10.1007/s00125-012-2562-9.
Homolya L, Fu D, Sengupta P, et al. PLoS One 2014; 9(3): e91921. https://doi.org/10.1371/journal.pone.0091921.
Saha AK, Xu XJ, Balon TW, et al. Cell Cycle 2011; 10(20): 3447-3451. https://doi.org/10.4161/cc.10.20.17886.
Filippatos TD, Liberopoulos EN, Elisaf MS. Ther Adv Endocrinol Metab 2015; 6(1): 29-41. https://doi.org/10.1177/2042018814558243.
Chang YK, Choi H, Jeong JY, et al. PLoS One 2016; 11(7): e0158810. https://doi.org/10.1371/journal.pone.0158810.
Zinman B, Wanner C, Lachin JM, et al. New Engl J Med 2015; 373(22): 2117-2128. https://doi.org/10.1056/NEJMoa1504720.