Diabetic Cardiomyopathy (DCM) is а frequent complication of Diabetes Mellitus (DM) and a major cause of mortality in DM patients. However, the pathogenesis of DCM remains poorly studied. In particular, disorganization of the T-system (the system of transverse invaginations of plasma membrane into the cell and their longitudinal connections) of cardiomyocytes is considered as an early marker of cardiac pathology of various etiology and as a potentially critical step in the development of DCM. Testing this suggestion was the main goal of the current investigation conducted in rat models (male Wistar rats) of short-term (1 month), streptozotocin-induced (STZ, 30 mg/kg body weight, single intraperitoneal injection) prediabetes and acute DM (PrDM and ADM). STZ-rats that developed hyperglycemia (random glucose > 11 mM) were considered as ADM-rats, while the remaining STZ-rats – as PrDM animals. Evaluation of structural integrity of the T-system was done using analysis of confocal images of the left ventricle epicardium myocytes of isolated hearts, stained with the Di-8-ANEPPS (20 µM). The results of the study have demonstrated that in the control hearts cardiomyocytes T-system is organized into regular networks of t-tubules, which run in parallel with Z-discs of the sarcomeres. Respectively, the frequency distributions of intervals between neighboring t-tubules (INT, measured along the major cell axis) peaked at 2 µm value with not more than 21% of INT (per cell) exceeding 3 µm cut-off. Only 4±3% of the control heart cardiomyocytes (274 cells, 4 rats) could be considered as deficient, according to this parameter (>21% occurrence of long INT). At the same time, in the hearts of ADM- and, unexpectedly, of PrDM-rats, the fractions of such deficient with regard to regularity of T-system cardiomyocytes were statistically significantly higher than those in control: 76±8% (ADM, 4 rats, 247 cells) and 48±13% (PrDM, 8 rats, 573 cells). Thus, our data confirm that structural changes in the T-system of the rat heart left ventricle cardiomyocytes develop early during ADM and also during prediabetic stages of DM. Evaluation of pathogenesis of these changes and their relevance to the increased risk of development of the heart failure in subjects with prediabetes remains to be studied. Supported by RFFI, award №19-015-00139.
Добрецов М. Г.