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

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.

Biomedicines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 43 ◽  
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Medhat Taha ◽  
Rami M. Elshazli ◽  
Raouf Fekry Bedir ◽  
...  

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).


2020 ◽  
Author(s):  
Jiajia Zhang ◽  
Ya-nan Wang ◽  
Tingting Jia ◽  
Haiyun Huang ◽  
Dongjiao Zhang ◽  
...  

Abstract Background: Type 2 diabetes mellitus (T2DM) has a harmful effect on the stability and osseointegration of dental implants. T2DM induces mitochondrial damage by inhibiting AMPK signaling, resulting in oxidative stress and poor osteogenesis in the peri-implant bone area. Genipin is a major component of gardenia fruits with strong antioxidant, anti-inflammation, and anti-diabetic actions, and it also can activate mitochondrial quality control via the AMPK pathway. The purpose of this study was to investigate the effects of genipin and insulin treatment on implant osseointegration in T2DM rats and explore the underlying mechanisms. Methods: Streptozotocin-induced diabetic rats received implant surgery in their femurs, and were then assigned to five groups that were subjected to different treatments for three months: control group, T2DM group, insulin-treated T2DM group (10 IU/kg), genipin-treated T2DM group (50 mg/kg), and the genipin and insulin combination-treated T2DM group. Then, we regularly assessed the weight and glucose levels of the animals. Rats were euthanized at three months after the implantation procedure, and the femora were harvested for microscopic computerized tomography analysis, biomechanical tests, and different histomorphometric assessment. Results: The results indicated that the highest blood glucose and oxidative stress levels were measured for the T2DM group, resulting in the poorest osseointegration. The combination-treated T2DM group mitigated hyperglycemia and normalized, reactivated AMPK signaling, and alleviated oxidative stress as well as reversed the negative effect of osseointegration. There were beneficial changes observed in the T2DM-genipin and T2DM-insulin groups, but these were less in comparison to the combination treatment group. Conclusion: Our study suggests that treatment with genipin in combination with insulin could be an effective method for promoting implant osseointegration in T2DM rats, which may be related to AMPK signaling.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jiajia Zhang ◽  
Ya-nan Wang ◽  
Tingting Jia ◽  
Haiyun Huang ◽  
Dongjiao Zhang ◽  
...  

Abstract Background Type 2 diabetes mellitus (T2DM) has a harmful effect on the stability and osseointegration of dental implants. T2DM induces mitochondrial damage by inhibiting AMPK signaling, resulting in oxidative stress and poor osteogenesis in the peri-implant bone area. Genipin is a major component of gardenia fruits with strong antioxidant, anti-inflammation, and antidiabetic actions, and it also can activate mitochondrial quality control via the AMPK pathway. The purpose of this study was to investigate the effects of genipin and insulin treatment on implant osseointegration in T2DM rats and explore the underlying mechanisms. Methods Streptozotocin-induced diabetic rats received implant surgery in their femurs and were then assigned to five groups that were subjected to different treatments for three months: control group, T2DM group, insulin-treated T2DM group (10 IU/kg), genipin-treated T2DM group (50 mg/kg), and the genipin and insulin combination-treated T2DM group. Then, we regularly assessed the weight and glucose levels of the animals. Rats were euthanized at 3 months after the implantation procedure, and the femora were harvested for microscopic computerized tomography analysis, biomechanical tests, and different histomorphometric assessment. Results The results indicated that the highest blood glucose and oxidative stress levels were measured for the T2DM group, resulting in the poorest osseointegration. The combination-treated T2DM group mitigated hyperglycemia and normalized, reactivated AMPK signaling, and alleviated oxidative stress as well as reversed the negative effect of osseointegration. There were beneficial changes observed in the T2DM-genipin and T2DM-insulin groups, but these were less in comparison to the combination treatment group. Conclusion Our study suggests that treatment with genipin in combination with insulin could be an effective method for promoting implant osseointegration in T2DM rats, which may be related to AMPK signaling.


2020 ◽  
Vol 24 (3) ◽  
pp. 174-184
Author(s):  
Dara Dastan ◽  
◽  
Iraj Salehi ◽  
Alireza Komaki ◽  
Alireza Gharib ◽  
...  

Introduction: Diabetes mellitus (DM) is one of the most frequent metabolic diseases that affect various body systems. Cognitive impairment caused by diabetes is gaining more acceptance and attention. In this study, we have investigated the effects of a traditionally herbal formulation (THF) on oxidative stress (OS) and cognitive deficits in type 2 diabetic rats. Methods: Thirty-six male Wistar rats were divided into six groups: control group, diabetic group, diabetic+100, 200 or 300mg/kg THF, diabetic+glibenclamide (G) 5mg/kg. Streptozotocin-nicotinamide was used to induce type-II diabetes mellitus. Spatial and passive avoidance learning and memory function were evaluated by Morris Water Maze (MWM), novel object recognition test (NORT) and open field test (OFT). The OS biomarkers were also analyzed. The THF was standardized using RP-HPLC according to phenolic and flavonoids compounds. Results: Indicated that in the diabetic treated (300mg/kg THF and G) vs. diabetic groups, body weight and insulin were significantly increased and the levels of fasting blood glucose significantly reduced. OS was improved in the treated (300mg/kg THF) groups. Furthermore, we noticed that diabetic treated groups (300mg/kg THF) vs. diabetes caused in significant decreases of the travelled distance and escape latency to find the hidden platform, also increased in the time spent and travelled distance in the target quadrant in MWM test, exploration time in NORT and total distance moved in OFT. Conclusion: These findings suggest that THF ameliorated learning and memory deficits in type 2 diabetic rats via reducing OS. THF can be used with a caution against human DM.


2020 ◽  
Vol 17 (6) ◽  
pp. 147916412096699
Author(s):  
Wenru Li ◽  
Chaonan Zhu ◽  
Tianheng Liu ◽  
Weifang Zhang ◽  
Xu Liu ◽  
...  

Aims: The objective of this study was to explore the effects of epigallocatechin-3-gallate (EGCG) on type 2 diabetes mellitus (T2DM). Main methods: Male Sprague–Dawley rats were allocated into six groups. The control group received a conventional diet. The diabetic group received a high-sucrose high-fat (HSHF) diet for 4 weeks and then was fasted and injected with streptozotocin (STZ); subsequently, the rats received a HSHF diet for another 4 weeks to develop diabetes. The four treatment groups were diabetic rats that received intragastric metformin (500 mg/kg/day) or EGCG (25, 50, and 100 mg/kg/day) for 10 weeks. All groups except the control group received a HSHF diet throughout the experiment. Several biochemical parameters such as fasting blood glucose (FBG), postprandial blood glucose (PBG), liver glycogen, muscle glycogen, fasting serum insulin (FSI), homeostasis model of insulin resistance (HOMA-IR), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), free fatty acids (FFA), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured to assess the effects of EGCG on glycemic control, insulin resistance, lipid profile, and oxidative stress. Furthermore, oxidative stress in pancreatic islet β cells was detected by dihydroethidium staining. Key findings: A HSHF diet and STZ injection induced T2DM, as indicated by changed blood glucose and body weight, which was accompanied by insulin resistance, an altered lipid profile, and oxidative stress. Interestingly, EGCG treatment dose-dependently recovered these indexes. Significance: EGCG successfully ameliorated glycemic control and insulin sensitivity while reducing the lipid profile and oxidative stress in a T2DM rat model.


2020 ◽  
Vol 45 (4) ◽  
pp. 397-404
Author(s):  
Tugba Gurpinar Çavuşoğlu ◽  
Ertan Darıverenli ◽  
Kamil Vural ◽  
Nuran Ekerbicer ◽  
Cevval Ulman ◽  
...  

AbstractObjectivesType 2 diabetes is a common metabolic disease and anxiety disorders are very common among diabetics. Buspirone is used in the treatment of anxiety, also having blood glucose-lowering effects. The aim of the study was to investigate the effects of buspirone on the glucose and lipid metabolism as well as vascular function in type 2 diabetic rats.MethodsA type 2-diabetic model was induced through a high-fat diet for eight weeks followed by the administration of low-dose streptozotocin (35 mg/kg, intraperitoneal) in rats. Buspirone was given at two different doses (1.5 mg/kg/d and 5 mg/kg/d) and combined with metformin (300 mg/kg/d). The fasting glucose and insulin levels, lipid profile were analyzed, and vascular response measured from the thoracic aorta was also evaluated.ResultsBoth doses of buspirone caused a significant improvement in fasting blood glucose levels. In particular, the buspirone treatment, combined with metformin, improved endothelial dysfunction and was found to be correlated with decreased nitrate/nitrite levels.ConclusionsBuspirone may be effective in the treatment of type 2 diabetes, either alone or in combination with other treatments, particularly in terms of endothelial dysfunction, inflammation and impaired blood glucose, and insulin levels.


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