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Abstract
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 µg/kg for 4 weeks, and (d) DM + SGLT2i as DM group with SGLT2 inhibitor (dapagliflozin) at a dose of 1 mg/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-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 < 0.05). Administration of either GLP1 analog or SGLT2i caused a significant improvement in all studied parameters (p < 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-α and TGF-β).
Highlights
Diabetes mellitus (DM) is a systemic metabolic disease, which is characterized by chronic hyperglycemia due to lack of insulin secretion, insulin action, or both [1,2]
The levels of blood glucose, homeostasis model assessment (HOMA), LDH and CK-MB were significantly attenuated in Diabetes Mellitus (DM) + sodium/glucose cotransporter 2 inhibitors (SGLT2i) and DM + GLP1 groups compared to the DM group, while insulin was significantly increased in treated groups compared to the DM group (p < 0.05)
There were no statistically significant differences between DM + SGLT2i and GLP1 groups in these parameters, except blood glucose, which was significantly lower in the DM + SGLT2i group than the DM + GLPT1 group (Table 1)
Summary
Diabetes mellitus (DM) is a systemic metabolic disease, which is characterized by chronic hyperglycemia due to lack of insulin secretion, insulin action, or both [1,2]. Biomedicines 2020, 8, 43 study demonstrated that 415 million adults are living with DM, and this number is projected to reach. 642 million by 2040 [3]. Type 2 DM (T2DM) is commonly associated with several cardiovascular complications such as coronary artery disease (CAD), stroke, and diabetic cardiomyopathy (DCM), which account for up to 65% of all deaths in diabetic patients [4]. DCM is defined as the presence of heart failure in absence of coronary artery disease [5]. DCM is associated with systolic and diastolic functions in which the prognosis is poor with an annual mortality of 15%–20%, reviewed in [6].
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