Cardiomyocyte T-System Remodeling in a Rat Model of Metabolic Syndrome

Heart failure of various etiologies, including diabetic cardiomyopathy (DCM), is a global problem. However, the features of DCM pathogenesis, including the role of the T-tubular system in this process, are not fully understood. The available literature data on T-system remodeling in diabetic rodent models are contradictory, with changes in this system being demonstrated in some of them already at the prediabetic stage. So, this work was aimed to assess changes in the T-system in a rat model of metabolic syndrome (MS) that precedes type 2 diabetes mellitus. MS was induced in Wistar rats by a high-carbohydrate (HC) and a combined high-carbohydrate high-fat (HCHF) diets for 10 weeks. The parameters to be finally estimated were body, abdominal fat, and heart weights, as well as fasting plasma glucose levels measured by a glucose tolerance test (GTT). The structure of the T-system was examined via confocal microscopy in isolated hearts stained with DI-8-ANEPPS. HCHF-fed rats developed more severe MS since their body and abdominal fat weights, as well as fasting plasma glucose levels, were significantly higher compared to the controls; moreover, GTT revealed the signs of glucose tolerance. HC-fed rats were characterized by a moderate MS, as manifested only in an increase in abdominal fat weight. The structural correlates of T-system remodeling were also found in HCHF-fed rats only, as manifested in a significant increase in the average interval between the rows of T-tubules. These findings differ from our results obtained in a model of type 1 prediabetes and diabetes. Thus, T-system remodeling in rat cardiomyocytes begins already at the stage of HCHF-induced MS and proceeds similarly to that described for type 2 diabetes, but differs from that in type 1 prediabetes and diabetes, suggesting different pathways of DCM pathogenesis in different diabetic types.