Investigation on the Effects of GLP1 analog and SGLT2 inhibitor against Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

2021 ◽  
pp. 1-20
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Medhat Taha ◽  
Rami M. Elshazli ◽  
Raouf Fekry Bedir ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Sglt2 Inhibitor ◽  
Diabetic Rats ◽  
Underlying Mechanisms ◽  
Type 2 Diabetic

scholarly journals Comparative Study of the Effects of GLP1 Analog and SGLT2 Inhibitor against Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

Biomedicines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 43 ◽  
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Medhat Taha ◽  
Rami M. Elshazli ◽  
Raouf Fekry Bedir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Caspase 3 ◽  
Sglt2 Inhibitor ◽  
Diabetic Rats ◽  
Tnf Α ◽  
Cardioprotective Effects ◽  
Underlying Mechanisms ◽  
Type 2 Diabetic

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).

Exercise and Stevia Rebaudiana (R) Extracts Attenuate Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

2020 ◽  
Vol 20 (7) ◽  
pp. 1117-1132
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Ismaeel Bin-Jaliah ◽  
Medhat Taha ◽  
Lashin S. Lashin
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Diabetic Cardiomyopathy ◽  
Caspase 3 ◽  
Stevia Rebaudiana ◽  
Diabetic Rats ◽  
Control Group ◽  
Underlying Mechanisms ◽  
Type 2 Diabetic

Background and Aims: In the current work, we studied the effects of exercise and stevia rebaudiana (R) extracts on diabetic cardiomyopathy (DCM) in type 2 diabetic rats and their possible underlying mechanisms. Methods: : Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group, b) DM group, type 2 diabetic rats received 2 ml oral saline daily for 4 weeks, c) DM+ Exercise, type 2 diabetic rats were treated with exercise for 4 weeks and d) DM+ stevia R extracts: type 2 diabetic rats received methanolic stevia R extracts. By the end of the experiment, serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB), cardiac histopathology, oxidative stress markers (MDA, GSH and CAT), myocardial fibrosis by Masson trichrome, the expression of p53, caspase-3, α-SMA and tyrosine hydroxylase (TH) by immunostaining in myocardial tissues were measured. Results: T2DM caused a significant increase in blood glucose, HOMA-IR index, serum CK-MB and LDH, myocardial damage and fibrosis, myocardial MDA, myocardial α-SMA, p53, caspase-3, Nrf2 and TH density with a significant decrease in serum insulin and myocardial GSH and CAT (p< 0.05). On the other hand, treatment with either exercise or stevia R extracts significantly improved all studied parameters (p< 0.05). Moreover, the effects of stevia R was more significant than exercise (p< 0.05). Conclusion: Both exercise and methanolic stevia R extracts showed cardioprotective effects against DCM and Stevia R offered more cardioprotective than exercise. This cardioprotective effect of these lines of treatment might be due to attenuation of oxidative stress, apoptosis, sympathetic nerve density and fibrosis and upregulation of the antioxidant transcription factor, Nrf2.

scholarly journals Effect of gamma-carboxylase inhibition on serum osteocalcin may be partially protective against developing diabetic cardiomyopathy in type 2 diabetic rats

2016 ◽  
Vol 13 (6) ◽  
pp. 405-417 ◽  
Author(s):  
Sarah Mahmoud Gamal ◽  
Nermeen Bakr Sadek ◽  
Laila Ahmed Rashed ◽  
Heba Mohamed Shawky ◽  
Maha Mohamed Gamal El-Din
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Diabetic Rats ◽  
Serum Osteocalcin ◽  
Type 2 Diabetic

Abstract 13376: Oral Treatment With a Zinc Complex of Acetylsalicylic Acid Prevents Diabetic Cardiomyopathy in a Rat Model of Type 2 Diabetes

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Sevil Korkmaz-Icöz ◽  
Samer Alsaid ◽  
Tamás Radovits ◽  
Shiliang Li ◽  
Mihály Ruppert ◽  
...  
Keyword(s):  
Oral Administration ◽  
Acetylsalicylic Acid ◽  
Diabetic Cardiomyopathy ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Increased Risk ◽  
Type 2 Diabetic

Introduction: Type 2 diabetic patients are at an increased risk of cardiomyopathy and heart failure is a major cause of death amongst these patients. Growing evidence indicates that proinflammatory cytokines can cause sustained development of insulin resistance and anti-inflammatory medications may reverse this process. Hypothesis: We investigated the effects of an oral administration of zinc and acetylsalicylic acid in the form of bis(aspirinato)zinc(II) complex Zn(ASA)2 on different aspects of cardiac damage in the Zucker diabetic rat (ZDF), an experimental model of type 2 diabetic cardiomyopathy. Methods: The nondiabetic control and the diabetic ZDF rats were pretreated orally with vehicle or Zn(ASA)2 for 24 days. At the age of 30-32 weeks, both the electrical activity and the left ventricular (LV) structural/functional parameters were assessed via electrocardiogram and pressure volume (PV) conductance catheter system. Results: The Zn(ASA)2 treatment significantly decreased the blood glucose concentration (39.6±3.1 vs 50.4±2.6 mM), normalized the impaired LV contractility index (Emax 3.7±0.4 vs 1.9±0.6 mmHg/μl), the passive LV stiffness (end diastolic PV relationship: 0.064±0.008 vs 0.084±0.014 mmHg/μl), and the diastolic dysfunction (LV end diastolic pressure: 6.5±0.6 vs 7.9±0.7 mmHg). Furthermore, the ECG revealed a restoration of the prolonged corrected QT intervals (63±3 vs 83±4 ms, p<0.05) by Zn(ASA)2. A histological examination revealed an increase in the cardiomyocytes transverse cross section area in diabetic rats compared to the controls, which was significantly decreased after Zn(ASA)2. Furthermore, a significant increase in fibrotic formation was observed in the diabetic rats compared to controls, and Zn(ASA)2 administration showed similar collagen content in the ZDF+Zn(ASA)2 rats and in the nondiabetics. A significant increase in the density of TUNEL positive cell nuclei in the diabetic hearts, indicating DNA fragmentation, was significantly decreased by Zn(ASA)2. Additionally, in the diabetic heart, Zn(ASA)2 significantly decreased nitrotyrosine formation. Conclusions: The oral administration of Zn(ASA)2 may have therapeutic potential with the aim of preventing cardiac complications in type 2 diabetic patients.

scholarly journals EFFECTS OF NANOCURCUMIN IN RATS WITH DIABETES INDUCED WITH STREPTOZOTOCIN AND NICOTINAMIDE: MRNA EXPRESSION OF B-TYPE NATRIURETIC PEPTIDE

2018 ◽  
Vol 10 (1) ◽  
pp. 175
Author(s):  
Maryam Ulfa ◽  
Dyah Suci Handayani ◽  
Hotlina Nainggolan ◽  
Wawaimuli Arozal
Keyword(s):  
Polymerase Chain Reaction ◽  
Mrna Expression ◽  
Natriuretic Peptide ◽  
Diabetic Cardiomyopathy ◽  
Heart Tissue ◽  
Diabetic Rats ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Type 2 Diabetic

Objective: This study aimed to determine the effects of nanocurcumin on cardiomyopathy, assessed by the expression of B-type natriuretic peptide(BNP) mRNA in heart tissue.Methods: Type 2 diabetic rats were induced with streptozotocin and nicotinamide. Nanocurcumin was orally administered (100 mg/kg/day)for 30 days. BNP-45 mRNA expression in the heart tissue was measured using quantitative reverse transcription-polymerase chain reaction andcalculated using the Livak method.Results: BNP-45 levels increased significantly (p<0.05) in diabetic rats compared with the normal group. Nanocurcumin treatment at a dose of100 mg/kg for 30 days significantly decreased BNP-45 expression levels (p<0.05) compared with diabetic rats without treatment.Conclusion: Nanocurcumin may be beneficial in inhibiting the progression of diabetic cardiomyopathy by suppressing the expression of BNP-45.

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