The activity of matrix metalloproteinases and the concentration of their tissue inhibitors in the blood serum of patients with type 2 diabetes mellitus, depending on the stage of compensation of the disease

Abstract

The aim of the study was to test the hypothesis on the possible reason for the decrease in the activity of matrix metalloproteinases (MMPs) as a consequence of the high concentration of their tissue inhibitors (TIMPs) in the blood serum of patients with type 2 diabetes mellitus (T2DM). Material and methods. In the experimental part of the article, we used the blood serum of patients under observation in the clinic of the Federal Research Center of Fundamental and Translational Medicine. According to the content of glycated hemoglobin (HbA1С) in blood serum, the patients were divided into 3 groups: at the stage of compensation (6.0–6.5 % HbA1С), at the stage of subcompensation (6.6–7.0 % HbA 1С) and decompensation (> 7.0 % HbA1С). The activity of MMPs 2 and 7 in blood serum samples was measured by a fluorimetric method using a fluorescent substrate specific for these MMPs. The concentration of TIMP-1 (inhibitor of all non-membrane-bound MMPs) and TIMP-2 (active against MMP-2 and -7) in blood serum were determined by enzyme immunoassay. Results and discussion. In patients with T2DM, the MMP-2 and -7 activities decreased, more pronouncedly at the stage of decompensation. An increase in the concentration of TIMP-1 was observed in the serum of all patients, while no significant changes in the content of TIMP-2 were found. At the stage of decompensation, a decrease in MMP activity was accompanied by a decrease in the content of insulin, C-peptide and a corresponding increase in the level of proinsulin. An inverse correlation was found between the concentrations of TIMP-1 and insulin in patients at the stage of decompensation of T2DM. It is assumed that the activity of MMP-2 and -7, in comparison with their inhibitors, forms stronger correlations with the parameters of carbohydrate metabolism.

Keywords

• type 2 diabetes mellitus
• tissue inhibitor of matrix metalloproteinases-2 and -7
• tissue inhibitor of matrix metalloproteinases-1 and -2