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Background: The present study investigated the possible cardioprotective effects of GLP1 and SGLT2i against diabetic cardiomyopathy (DCM) in type 2 diabetic rats and the possible underlying mechanisms. DCM is defined as the presence of heart failure in absence of coronary artery disease. Methods: Thirty-two male Sprague Dawley rats were randomly subdivided into 4 equal groups; a) control group, b) DM group, type 2 diabetic rats with saline daily for 4 weeks, c) DM+ GLP1, as DM group with GLP1 analogue (liraglutide) at a dose of 75 µg/kg for 4 weeks, and d) DM+ SGLT2i: as DM group with SGLT2 inhibitor (dapagliflozin) at a dose of 1mg/kg for 4 weeks. By the end of treatment (4 weeks), serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB) were measured. Also, the cardiac histopathology, myocardial oxidative stress markers (MDA, GSH and CAT) and norepinephrine (NE), myocardial fibrosis, the expression of caspase-3, TGF-β, TNF-α and tyrosine hydroxylase (TH) in myocardial tissues were measured. Results: T2DM caused significant increase in serum glucose, HOMA-IR, serum CK-MB and LDH (p< 0.05). Also, DM caused significant myocardial damage and fibrosis, elevation of myocardial MDA, NE with upregulation of myocardial caspase-3, TNF-α, TGF-β and TH and significant decrease in serum insulin and myocardial GSH and CAT (p

The present study investigated the possible cardioprotective effects of GLP1 and SGLT2i against diabetic cardiomyopathy (DCM) in type 2 diabetic rats and the possible underlying mechanisms. Methods: Thirty-two male Sprague Dawley rats were randomly subdivided into 4 equal groups: a) control group, b) DM group, type 2 diabetic rats with saline daily for 4 weeks, c) DM+ GLP1, as DM group with GLP1 analogue (liraglutide) at a dose of 75 &micro, g/kg for 4 weeks, and d) DM+ SGLT2i as DM group with SGLT2 inhibitor (dapagliflozin) at a dose of 1mg/kg for 4 weeks. By the end of treatment (4 weeks), serum blood glucose, homeostasis model assessment insulin resistance (HOMA-IR), insulin, and cardiac enzymes (LDH, CK-MB) were measured. Also, the cardiac histopathology, myocardial oxidative stress markers (malondialdehyde (MDA), glutathione (GSH) and CAT) and norepinephrine (NE), myocardial fibrosis, the expression of caspase-3, TGF-&beta, TNF-&alpha, and tyrosine hydroxylase (TH) in myocardial tissues were measured. Results: T2DM caused significant increase in serum glucose, HOMA-IR, serum CK-MB, and LDH (p &lt, 0.05). Also, DM caused significant myocardial damage and fibrosis, elevation of myocardial MDA, NE with upregulation of myocardial caspase-3, TNF-&alpha, TGF-&beta, and TH, and significant decrease in serum insulin and myocardial GSH and CAT (p &lt, 0.05). Administration of either GLP1 analog or SGLT2i caused a significant improvement in all studied parameters (p &lt, 0.05). Conclusion: We concluded that both GLP1 and SGLT2i exhibited cardioprotective effects against DCM in T2DM, with the upper hand for SGLT2i. This might be due to attenuation of fibrosis, oxidative stress, apoptosis (caspase-3), sympathetic nerve activity, and inflammatory cytokines (TNF-&alpha, and TGF-&beta, ).

Background: Diabetic nephropathy (DN) has become one of the most common causes of end stage renal disease (ESRD). Hyperglycemia induces oxidative stress in renal tubular epithelial cells that initiate tubulointerstitial fibrosis, which is a characteristic feature of diabetic nephropathy that becomes progressively complicated by renal failure. Aim: To assess the effect of spironolactone (SPL) on WT-1 protein expression and ultrastructural changes associated with the progression of experimental diabetic nephropathy (DN).Methods: Forty female albino rats were divided into five groups. Group I (control group), Group II (untreated diabetic rats), Group III (insulin-treated diabetic rats), Group IV (spironolactone-treated diabetic rats) and Group V (insulin and spironolactone-treated diabetic rats). At the 4th and 8th weeks, 4 rats from each group were sacrificed and renal tissue and blood samples were obtained. The rats were anaesthetized using ether inhalation. Each kidney was longitudinally divided and processed for immunohistochemical analysis with rabbit polyclonal anti-WT-1 Antibody and electron microscopic examination.Results: Treatment of STZ-induced diabetic rats with insulin and spironolactone (Group V) showed improvement in renal corpuscles as well as their capsular space, the basement membrane became normal with preserved minor and major processes and subpodocytic space, most of the proximal convoluted tubules retained their brush border, and their cells showed normal euchromatic nuclei and scattered mitochondria with apical microvilli, which is similar to the findings of the control group. Quantitative analyses showed significant increase in area of fibrosis and focal thickening of the glomerular basement membrane in non-SPL treated groups. There was a marked decrease in proteinuria compared to other treated groups. The results were better after 8 weeks compared to those after 4 weeks.Conclusions: The administration of SPL significantly prevented the extent of interstitial fibrosis in the diabetic kidney.