scholarly journals Kv1.3 Channel Blockade Improves Inflammatory Profile, Reduces Cardiac Electrical Remodeling, and Prevents Arrhythmia in Type 2 Diabetic Rats

2021 ◽  
Author(s):  
Julián Zayas-Arrabal ◽  
Amaia Alquiza ◽  
Ainhoa Rodríguez-de-Yurre ◽  
Leyre Echeazarra ◽  
Víctor Fernández-López ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiac Arrhythmia ◽  
Torsade De Pointes ◽  
Diabetic Rats ◽  
Electrical Remodeling ◽  
Low Grade ◽  
Channel Blockade ◽  
Kv1.3 Channel ◽  
Type 2 Diabetic

Abstract Purpose Kv1.3 channel regulates the activity of lymphocytes, macrophages, or adipose tissue and its blockade reduces inflammatory cytokine secretion and improves insulin sensitivity in animals with metabolic syndrome and in genetically obese mice. Thus, Kv1.3 blockade could be a strategy for the treatment of type 2 diabetes. Elevated circulating levels of TNFα and IL-1b mediate the higher susceptibility to cardiac arrhythmia in type 2 diabetic rats. We hypothesized that Kv1.3 channel blockade with the psoralen PAP1 could have immunomodulatory properties that prevent QTc prolongation and reduce the risk of arrhythmia in type 2 diabetic rats. Methods Type 2 diabetes was induced to Sprague-Dawley rats by high-fat diet and streptozotocin injection. Diabetic animals were untreated, treated with metformin, or treated with PAP1 for 4 weeks. Plasma glucose, insulin, cholesterol, triglycerides, and cytokine levels were measured using commercial kits. ECG were recorded weekly, and an arrhythmia-inducing protocol was performed at the end of the experimental period. Action potentials were recorded in isolated ventricular cardiomyocytes. Results In diabetic animals, PAP1 normalized glycaemia, insulin resistance, adiposity, and lipid profile. In addition, PAP1 prevented the diabetes-induced repolarization defects through reducing the secretion of the inflammatory cytokines IL-10, IL-12p70, GM-CSF, IFNγ, and TNFα. Moreover, compared to diabetic untreated and metformin-treated animals, those treated with PAP1 had the lowest risk of developing the life-threatening arrhythmia Torsade de Pointes under cardiac challenge. Conclusion Kv1.3 inhibition improves diabetes and diabetes-associated low-grade inflammation and cardiac electrical remodeling, resulting in more protection against cardiac arrhythmia compared to metformin.

Blockade of Renin Angiotensin System Ameliorates the Cardiac Arrhythmias and Sympathetic Neural Remodeling in Hearts of Type 2 DM Rat Model

2020 ◽  
Vol 20 (3) ◽  
pp. 464-478 ◽  
Author(s):  
Yomna M. Yehya ◽  
Abdelaziz M. Hussein ◽  
Khaled Ezam ◽  
Elsayed A. Eid ◽  
Eman M. Ibrahim ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiac Arrhythmias ◽  
Sympathetic Nerve ◽  
Renin Angiotensin System ◽  
Diabetic Rats ◽  
Angiotensin System ◽  
Type 2 Dm ◽  
Type 2 Diabetic ◽  
Diabetes Induction

Objectives:: The present study was designed to investigate the effects of renin angiotensin system (RAS) blockade on cardiac arrhythmias and sympathetic nerve remodelling in heart tissues of type 2 diabetic rats. Methods:: Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group: normal rats, b) DM group; after type 2 diabetes induction, rats received 2ml oral saline daily for 4 weeks, c) DM+ ACEi: after type 2 diabetes induction, rats were treated with enalapril (10 mg/kg, orally for 4 weeks) and d) DM+ ARBs: after type 2 diabetes induction, rats were treated with losartan (30 mg/kg, orally for 4 weeks). Results:: In type 2 diabetic rats, the results demonstrated significant prolongation in Q-T interval and elevation of blood sugar, HOMA-IR index, TC, TGs, LDL, serum CK-MB, myocardial damage, myocardial MDA, myocardial norepinephrine and tyrosine hydroxylase (TH) density with significant reduction in serum HDL, serum insulin and myocardial GSH and CAT. On the other hand, blockade of RAS at the level of either ACE by enalapril or angiotensin (Ag) receptors by losartan resulted in significant improvement in ECG parameters (Q-T), cardiac enzymes (CK-MB), cardiac morphology, myocardial oxidative stress (low MDA, high CAT and GSH) and myocardial TH density. Conclusions:: RAS plays a role in the cardiac sympathetic nerve sprouting and cardiac arrhythmias induced by type 2 DM and its blockade might have a cardioprotective effect via attenuation of sympathetic nerve fibres remodelling, myocardial norepinephrine contents and oxidative stress.

scholarly journals An anxiolytic drug buspirone ameliorates hyperglycemia and endothelial dysfunction in type 2 diabetic rat model

2020 ◽  
Vol 45 (4) ◽  
pp. 397-404
Author(s):  
Tugba Gurpinar Çavuşoğlu ◽  
Ertan Darıverenli ◽  
Kamil Vural ◽  
Nuran Ekerbicer ◽  
Cevval Ulman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Insulin Levels ◽  
Type 2 Diabetic

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.

scholarly journals Protective effect of crocin and voluntary exercise against oxidative stress in the heart of high-fat diet-induced type 2 diabetic rats

2016 ◽  
Vol 103 (4) ◽  
pp. 459-468 ◽  
Author(s):  
V Ghorbanzadeh ◽  
M Mohammadi ◽  
G Mohaddes ◽  
H Dariushnejad ◽  
L Chodari ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
High Fat Diet ◽  
Critical Role ◽  
Diabetic Rats ◽  
Voluntary Exercise ◽  
High Fat ◽  
The Impact ◽  
Type 2 Diabetic

Background Oxidative stress plays a critical role in the pathogenesis and progression of type 2 diabetes and diabetic-associated cardiovascular complications. This study investigated the impact of crocin combined with voluntary exercise on heart oxidative stress indicator in high-fat diet-induced type 2 diabetic rats. Materials and methods Rats were divided into four groups: diabetes, diabetic-crocin, diabetic-voluntary exercise, diabetic-crocin-voluntary exercise. Type 2 diabetes was induced by high-fat diet (4 weeks) and injection of streptozotocin (intraperitoneally, 35 mg/kg). Animals received crocin orally (50 mg/kg); voluntary exercise was performed alone or combined with crocin treatment for 8 weeks. Finally, malondialdehyde (MDA), activity of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured spectrophotometrically. Results Treatment of diabetic rats with crocin and exercise significantly decreased the levels of MDA (p < 0.001) and increased the activity of SOD, GPx, and CAT compared with the untreated diabetic group. In addition, combination of exercise and crocin amplified their effect on antioxidant levels in the heart tissue of type 2 diabetic rats. Conclusion We suggest that a combination of crocin with voluntary exercise treatment may cause more beneficial effects in antioxidant defense system of heart tissues than the use of crocin or voluntary exercise alone.

Anti-inflammatory and insulin secretory activity in experimental type-2 diabetic rats treated orally with magnesium

2018 ◽  
Vol 29 (5) ◽  
pp. 507-514 ◽  
Author(s):  
Abayomi Oluwatosin Ige ◽  
Olanrewaju Amos Ajayi ◽  
Eunice Olufunke Adewoye
Keyword(s):  
Insulin Resistance ◽  
Serum Insulin ◽  
Density Lipoprotein ◽  
Diabetic Rats ◽  
Low Grade ◽  
Control Serum ◽  
Experimental Type ◽  
Anti Inflammatory ◽  
Type 2 Diabetic

Abstract Background Diabetes mellitus causes low-grade chronic inflammation which leads to the development of long-term complications. Oral magnesium (Mg) intake amongst other effects was reported to reduce the levels of inflammatory markers. This study investigated the anti-inflammatory and insulin secretory activities in experimental type-2 diabetic rats (n=32) orally treated with Mg. Methods Experimental type-2 diabetic rats were induced with high fat diet and alloxan (50 mg/kg, single i.p.) for over 10 weeks prior to the experimental procedures. Male Wistar rats were divided into 4 equal groups: control, untreated experimental diabetics, and experimental diabetics treated orally with either metformin (Met) (250 mg/kg), or Mg (250 mg/kg), respectively, for 14 days. The blood glucose (BG) levels were monitored before experimental induction of diabetes and thereafter on days 1, 7, 10, and 14, respectively. Serum insulin, C-reactive protein (CRP), interleukin-6 (IL-6), and lipid profile were assessed using laboratory kits while pancreatic beta cell function (BCF) and insulin resistance were estimated using homeostasis model assessment equations. Results Significant increase in the BG level was observed in all experimental diabetic groups on day 1 compared to controls. On day 14, BG, BCF, triglyceride, cholesterol, and low-density lipoprotein levels were increased while the high-density lipoprotein level was reduced in untreated diabetics compared to other groups. Insulin and insulin resistance were increased in all groups compared to control. Serum insulin and IL-6 were reduced while CRP was elevated in diabetic treated groups (Met and Mg) compared to untreated diabetics. Conclusions This study shows a hypoglycemic, lipid regulatory, insulin stimulatory, and anti-inflammatory effect of oral Mg treatment in experimental type-2 diabetic rats.

UPLC-MS based metabolite profiles of two major bioactive components in herb pair scutellaria–coptis metabolized by intestinal bacteria derived from healthy rats and rats with type 2 diabetes

2015 ◽  
Vol 7 (13) ◽  
pp. 5574-5582 ◽  
Author(s):  
Le-yue Du ◽  
Da-wei Qian ◽  
Er-xin Shang ◽  
Shu Jiang ◽  
Pei Liu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Intestinal Bacteria ◽  
Diabetic Rats ◽  
Bioactive Components ◽  
Metabolite Profiles ◽  
Type 2 Diabetic

This study describes the metabolites of two components in scutellaria–coptis metabolized by intestinal bacterial of healthy rats and type 2 diabetic rats.

scholarly journals Gymnemic acid, a potent antidiabetic agent protects skeletal muscle from hyperglycemia mediated oxidative stress and apoptotic events in High fat and High fructose diet fed adult rats

2020 ◽  
Vol 11 (2) ◽  
pp. 1526-1538
Author(s):  
Porkodi Karthikeyan ◽  
Lakshmi Narasimhan Chakrapani ◽  
Thangarajeswari Mohan ◽  
Bhavani Tamilarasan ◽  
Pughazhendi Kannan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Diabetic Rats ◽  
High Fat ◽  
Gymnemic Acid ◽  
High Fructose ◽  
Type 2 Diabetic

Type 2 diabetes is delineated by impaired metabolic flexibility, and intramyocellular lipid accumulation, causing insulin resistance, particularly in skeletal muscle by reducing insulin-stimulated glucose uptake. High-fat diet and high fructose (HFD and HF) administration in rodents bestows a model for hyperlipidemia, insulin resistance, and Type 2 diabetes. The current study is focused on elucidating the role of Gymnemic acid in combating hyperglycemia mediated oxidative stress and apoptotic events in the skeletal muscle of HFD and HF induced Type 2 diabetes in Wistar albino rats by boosting antioxidant defense system. Gymnemic acid, a saponin of triterpene glycoside contained in leaves of Gymnema Sylvestre, has potent anti-diabetic properties. Treatment with Gymnemic acid restored the antioxidant status (Gpx, SOD, CAT, GR, Vit C & Vit E) with significant (p<0.05) decrease in free radical levels and reinvigorated the expression of apoptotic and antiapoptotic proteins in Type 2 diabetic rats. Histopathological data demonstrate that oral administration of Gymnemic acid protects skeletal muscle fibers from an oxidative niche in HFD and HF in Type 2 diabetic rats. In accordance with this, Gymnemic acid might be regarded as a promising therapeutic agent against Type 2 diabetes, thereby restoring skeletal muscle integrity and function.

scholarly journals Effects of Hydrogen Sulfide on Carbohydrate Metabolism in Obese Type 2 Diabetic Rats

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 190 ◽  
Author(s):  
Sevda Gheibi ◽  
Sajad Jeddi ◽  
Khosrow Kashfi ◽  
Asghar Ghasemi
Keyword(s):  
Type 2 Diabetes ◽  
Hydrogen Sulfide ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Carbohydrate Metabolism ◽  
Serum Insulin ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Type 2 Diabetic

Hydrogen sulfide (H2S) is involved in the pathophysiology of type 2 diabetes. Inhibition and stimulation of H2S synthesis has been suggested to be a potential therapeutic approach for type 2 diabetes. The aim of this study was therefore to determine the effects of long-term sodium hydrosulfide (NaSH) administration as a H2S releasing agent on carbohydrate metabolism in type 2 diabetic rats. Type 2 diabetes was established using high fat-low dose streptozotocin. Rats were treated for 9 weeks with intraperitoneal injections of NaSH (0.28, 0.56, 1.6, 2.8, and 5.6 mg/kg). Serum glucose was measured weekly for one month and then at the end of the study. Serum insulin was measured before and after the treatment. At the end of the study, glucose tolerance, pyruvate tolerance and insulin secretion were determined and blood pressure was measured. In diabetic rats NaSH at 1.6–5.6 mg/kg increased serum glucose (11%, 28%, and 51%, respectively) and decreased serum insulin, glucose tolerance, pyruvate tolerance and in vivo insulin secretion. In controls, NaSH only at 5.6 mg/kg increased serum glucose and decreased glucose tolerance, pyruvate tolerance and insulin secretion. Chronic administration of NaSH in particular at high doses impaired carbohydrate metabolism in type 2 diabetic rats.

scholarly journals Effect of Rosmarinic Acid and Sinapic Acid on Oxidative Stress Parameters in the Cardiac Tissue and Serum of Type 2 Diabetic Female Rats

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 579 ◽  
Author(s):  
Maria Zych ◽  
Weronika Wojnar ◽  
Sławomir Borymski ◽  
Katarzyna Szałabska ◽  
Piotr Bramora ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Cardiac Tissue ◽  
Sinapic Acid ◽  
Diabetic Rats ◽  
Female Rats ◽  
Oxidative Stress Parameters ◽  
Type 2 Diabetic ◽  
Stress Parameters

Cardiovascular diseases are one of the most common complications of type 2 diabetes. They are considered the leading cause of death among diabetics. One of the mechanisms underlying diabetic cardiovascular complications is oxidative stress. Many phenolic acids are regarded as antioxidants. The aim of the study was to investigate the effect of rosmarinic acid (RA) and sinapic acid (SA) on oxidative stress parameters in the cardiac tissue and serum of type 2 diabetic female rats. Additionally, the effect of these compounds on glucose homeostasis and lipid profile in the serum was evaluated. Type 2 diabetes was induced with high-fat diet and streptozotocin. RA at the doses of 10 and 50 mg/kg and SA at the doses of 5 and 25 mg/kg were administrated orally for 28 days. Untreated diabetic rats exhibited unfavorable changes in glucose metabolism and lipid profile. Changes in the enzymatic and non-enzymatic markers indicated the onset of oxidative stress in these animals. The results showed that the higher doses of the tested phenolic acids—50 mg/kg of RA and 25 mg/kg of SA—revealed beneficial effects on oxidative stress in the cardiac tissue of diabetic rats.

Effect of Ginkgo Biloba Extract on Contractility Enhancement of Diaphragm of Rats with Type 2 Diabetes

2014 ◽  
Vol 989-994 ◽  
pp. 1015-1019
Author(s):  
Xu Sheng Li ◽  
Ren Yan Wu ◽  
Ye Hu
Keyword(s):  
Type 2 Diabetes ◽  
Ginkgo Biloba ◽  
Ginkgo Biloba Extract ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Control Group ◽  
Metabolism Enzymes ◽  
Type 2 Diabetic

To investigate the effects of Ginkgo biloba extract (GbE) on the activities of energy metabolism enzymes and contraction capacity of diaphragm from type 2 diabetic rats. Forty SD mile rats were randomly divided into normal control group (n=10) and model group (n=30). Type 2 diabetes models were induced by feeding with high-sucrose-high-fat diet and intraperitoneal injecting 25mg/kg streptozotocin. 20 successful models were rearranged to two groups: diabetic group and GbE treatment group, 10 rats in each. Then the saline and 8mg·kg-1·d-1 of GbE were respectively intraperitoneal injected, once a day continuously for 8 weeks. Then diaphragm contractility was assessed using Peak twitch tension (Pt), Maximum tetanic tension (P0) and fatigue index (FI) in vitro diaphragm strip preparations. Cytochrome oxidase (CCO), lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in diaphragm were detected and the varieties of diaphragm ultrastructure were observed. Compared with control group, Pt, P0 and FI in diabetic group decreased significantly (P < 0.01); the activity of CCO, LDH and SDH in the tissues was obviously reduced than those in control group (P < 0.01). The ultrastructure in diabetic group under electron microscope indicated that diaphragm mitochondrions swelled and degenerated. The above changes were inhibited by GbE. GbE can enhance contraction capacity of diaphragm from type 2 diabetic rats by increasing the aerobic oxidation capacity, glycolytic capacity and the function of respiratory chain.

scholarly journals Effect of Eight Weeks Resistance Training On Gene Expression of TNF-Α and IL10 in the Heart of Type II Diabetic Male Rats

2019 ◽  
Author(s):  
Zahra Soltanian ◽  
Behnaz Vanaky ◽  
Nasrin Ramezani ◽  
Nader Shakeri ◽  
Zahra Shams ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Resistance Training ◽  
Training Group ◽  
Heart Tissue ◽  
Diabetic Rats ◽  
Male Rats ◽  
Inflammatory Factors ◽  
Tnf Α ◽  
Type 2 Diabetic

Introduction: Type 2 diabetes has many complications, including cardiovascular disease, which is associated with an increase in inflammatory biomarkers. Research has shown that physical activity can reduce inflammatory factors and improve cardiovascular disease. The purpose of this study was to investigate the effect of resistance exercise on some of the inflammatory and anti-inflammatory factors in the heart tissue of type 2 diabetic rats. Methods: In this study, 18 male rats were selected. Rats were diabetic with nicotinamide and streptozotocin (stz) and then randomly divided into 2 groups of control (n=9) and training (n=9). The training group performed a resistance training program for 8 weeks, 5 days a week. Measurement of TNF-α and IL10 expression in the heart tissue was determined using the one step SYBR TAKARA single-step kit. To compare the difference between the mean of variables between exercise and control groups, independent t-test and t-test were used also to determine the effect of diabetes induction on variables. To determine the relationship between variables, Pearson correlation coefficient and separation correlation coefficient were used. Data were analyzed by SPSS software version 22. Results: The results showed that the insulin resistance index decreased significantly in the training group compared to the control group. On the other hand, the expression of TNF-α gene decreased and IL10 showed a significant increase (α≤0.05). Conclusion: The results indicate that resistance training may be effective in modulating the inflammatory factors of TNF-α and IL10 in the heart tissue of type 2 diabetic rats. Type 2 diabetes, Heart, Resistance training, Inflammatory factors.

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