The mirna-126 content in the blood serum of patients with type 2 diabetes after treatment with certain hypoglycemic drugs

Abstract

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.