Thesis (M.Sc.) - Cairo University - Faculty of Medicine - Department of Physiology

Background: Diabetic cardiomyopathy (DCM) is myocardial dysfunction in absence of significant coronary artery disease, hypertension or valvular disease. There is accumulating evidence to suggest a role of vitamin D in the protection against the development of DCM. Aim of the work: Our study was designed to study and compare the role of vitamin D and metformin supplementation on DCM in type 2 diabetic rat. Results: The present findings revealed development DCM in diabetic rats with hyperglycemia and dyslipidemia with a significant increased insulin levels and HOMA IR in diabetic rats. A significant decrease in VDR, beclin I and SERCAII gene expression in cardiac tissues of diabetic rats was recorded. Treatment of diabetes with metformin, vitamin D or both, improved the cardiac functions and resulted in a significant improvement of glycemic control, lipid metabolism and a significant increase in the expression of SERCA2, Beclin 1 and VDR. Histopathological examination showed collagen fibers deposition. in hearts of diabetic rats, that was decreased by treatment with metformin, vitamin D or both. Conclusion: Our results showed that vitamin D or metformin administration to the diabetic rats improved the functional performance of the hearts, through its effects on lipid profile and glycemic control. Vitamin D acts as antifibrotic agent and also through increases autophagy, Ca2+ homeostasis was improved and increases the expression of SERCAII in cardiac tissue and cause upregulation of vitamin D receptor in the heart. These results were confirmed by the reduction of biomarkers of DCM and histopathological examination. Both drugs in combination resulted in synergistic action as regard most of measured parameters.

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