Comparison of myocardial structural and molecular changes in rat models of type 1 and type 2 diabetes mellitus

Objectives: Cardiovascular complications are one of the main causes of mortality in diabetes mellitus (DM). There is obvious evidence demonstrating that DM leads to structural and functional changes at the level of the myocardium. In this study, we investigated and compared myocardial structural and molecular changes in rat models of type-1 and type-2 DM. Methods: Type-1 DM was induced in Sprague-Dawley rats by single injection of streptozotocin (60mg/kg, i.p.). Control rats receive only vehicle. Experiments were performed 8 wk after the confirmation of diabetes. For type-2 DM, Zucker-diabetic fatty (ZDF) and ZDF-lean rats were used and experiments were performed at the age of 30–32 wk. Heart samples were stained with hematoxylin-eosin and immunohistochemical analysis was performed for nitrotyrosine. TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) was used for detection of DNA-strand breaks. Different gene expression analysis was performed by quantitative real-time polymerase chain reaction. Results: Histopathological examination showed the characteristics of diabetic cardiomyopathy. DNA-breakage and nitro-oxidative stress were significantly more pronounced in type-1 compared to type-2 DM. mRNA-expression for α-MHC was significantly decreased whereas β-MHC and endothelin-1 mRNA-level was increased in both diabetic compared to corresponding control-groups. These alterations were more pronounced in type-1 DM. TGF-β1 and ANF mRNA-level was only up-regulated in type-2, whereas c-fos and c-jun only in type-1 DM. Moreover, endothelial NOS, collagen I and III was only down-regulated in type-1 DM. Conclusions: Our results show that rat model of type-1 DM is associated with significantly higher structural and molecular changes compared with the type-2 DM.