THE miRNA-126 CONTENT IN THE BLOOD SERUM OF PATIENTS WITH TYPE 2 DIABETES AFTER TREATMENT WITH CERTAIN HYPOGLYCEMIC DRUGS
Keywords:type 2 diabetes, miRNA-126, dapagliflozin, insulin, metformin, glycazide
MiRNAs are small endogenous non-coding RNAs involved in numerous processes of gene expression regulation. The association of endothelial miRNA-126 with type 2 diabetes mellitus (T2DM) has recently been established. Studies have shown a marked decrease of miRNA-126 in patients with type 2 diabetes. Aim. The expression profile of miRNA-126 in the circulation was analyzed in order to develop new approaches to predict the development and progression of diabetes. In the current study, the level of circulating miRNA-126 was studied in patients with T2DM under treatment with various hypoglycemic drugs. Materials and methods. The profile of circulating miRNA-126 was evaluated in a pilot study of 12 people: 6 healthy volunteers and 6 patients with type 2 diabetes. To determine the relative expression of miRNAs, the semi-quantitative real-time PCR was used. U6 snRNA encoding small nuclear RNA was used as a reference. Results. Combined treatment with dapagliflozin, insulin and metformin raises the amount of miRNA-126 to the control level that may be explained by a decrease in glucose concentration under the influence of these drugs. Dapagliflozin increases the miRNA-126 content by more than 4 times, compared with the control. It was also shown that treatment with dapagliflozin almost 2 times reduces the level of endothelin-1 (ET-1) in the blood of patients with diabetes, which indicates a significant effect of the drug on endothelial function. The effect of dapagliflozin in combination with metformin and insulin on the expression of miRNA-126 was significantly lower, which may be explained by competitive relationships between hypoglycemic drugs relative to the endothelium. Treatment of patients with biguanides did not lead to a significant decrease in the amount of ET-1, compared with the average level of endothelin in diabetes. Glyclazide monotherapy also increased the expression of miRNA-126 almost 3 times. Conclusion. Thus, the level of microRNA-126 circulating in the blood can be used as a diagnostic marker of endothelial dysfunction in type 2 diabetes. Determining the content of miRNA-126 may also be useful for evaluating the effectiveness of diabetes treatment with hypoglycemic agents.
Zampetaki A, Kiechl S, Drozdov I, et al. Circ Res 2010; 107: 810-817. https://doi.org/10.1161/CIRCRESAHA.110.226357.
Ortega FJ, Mercader JM, Moreno-Navarrete JM, et al. Diabetes Care 2014; 37(5): 1375-1383. https://doi.org/10.2337/dc13-1847.
Tron'ko ND, Pushkarev VM Sokolova LK, et al. Molekuljarnye mehanizmy patogeneza saharnogo diabeta i ego oslozhnenij, Kiev, 2018: 264 p.
Mathieson W, Betsou F, Myshunina T, et al. J Clin Pathol 2016; 69(12): 1105-1108.
Livak KJ, Schmittgen TD. Methods 2001; 25: 402-408. https://doi.org/10.1006/meth.2001.1262.
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. N Engl J Med 2015; 373(22): 2117-2128.
Sugiyama S, Jinnouchi H, Kurinami N, et al. Intern Med 2018; 57: 2147-2156. https://doi.org/10.2169/internalmedicine.0701-17.
Solini A, Giannini L, Seghieri M, et al. Cardiovasc Diabetol 2017; 16: 138. https://doi.org/10.1186/s12933-017-0621-8.
Ott C, Jumar A, Striepe K, et al. Cardiovasc Diabetol 2017; 16: 26. https://doi.org/10.1186/s12933-017-0510-1.
Aquilante CL. Expert Rev Cardiovasc Ther 2010; 8(3): 359-372. https://doi.org/10.1586/erc.09.154.
Hirst JA, Farmer AJ, Dyar A, et al. Diabetologia 2013; 56: 973-984. https://doi.org/10.1007/s00125-013-2856-6.
Simard JM, Kahle KT, Gerzanich V. J Neurosurg 2010; 113(3): 622-629. https://doi.org/10.3171/2009.11.JNS081052.
Rosenstock J, Marx N, Kahn SE, et al. Diab Vasc Dis Res 2013; 10(4): 289-301. https://doi.org/10.1177/1479164112475102.
Li Y, Zhou Q, Pei C, et al. J Vasc Res 2016; 53: 94-104. https://doi.org/10.1159/000448713.
Olivieri F, Spazzafumo L, Bonafи M, et al. Oncotarget. 2015; 6: 35372-35382. https://doi.org/10.18632/oncotarget.6164.
Mormile R. Cardiovasc Endocrinol Metab 2018; 7(3): 68-69. https://doi.org/10.1097/XCE.0000000000000156.
Grieco GE, Brusco N, Licata G, et al. Int J Mol Sci 2019; 20: 6358. https://doi.org/10.3390/ijms20246358.
Togliatto G; Trombetta A; Dentelli P; et al. Diabetes 2015; 64: 1370-1382. https://doi.org/10.2337/db14-0991.
Pushkarev VM, Sokolova LK, Pushkarev VV, Tron'ko ND. Probl endokryn patologii' 2016; 3: 77-90.