Beneficial effects of verapamil in diabetic cardiomyopathy

Diabetes ◽  
1988 ◽  
Vol 37 (7) ◽  
pp. 936-942 ◽  
Author(s):  
N. Afzal ◽  
P. K. Ganguly ◽  
K. S. Dhalla ◽  
G. N. Pierce ◽  
P. K. Singal ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Beneficial Effects

scholarly journals FGF1ΔHBS prevents diabetic cardiomyopathy by maintaining mitochondrial homeostasis and reducing oxidative stress via AMPK/Nur77 suppression

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Dezhong Wang ◽  
Yuan Yin ◽  
Shuyi Wang ◽  
Tianyang Zhao ◽  
Fanghua Gong ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Metabolic Regulation ◽  
Cardiac Injury ◽  
Serum Levels ◽  
Ros Generation ◽  
Dependent Manner ◽  
Cardiac Tissues ◽  
Beneficial Effects

AbstractAs a classically known mitogen, fibroblast growth factor 1 (FGF1) has been found to exert other pleiotropic functions such as metabolic regulation and myocardial protection. Here, we show that serum levels of FGF1 were decreased and positively correlated with fraction shortening in diabetic cardiomyopathy (DCM) patients, indicating that FGF1 is a potential therapeutic target for DCM. We found that treatment with a FGF1 variant (FGF1∆HBS) with reduced proliferative potency prevented diabetes-induced cardiac injury and remodeling and restored cardiac function. RNA-Seq results obtained from the cardiac tissues of db/db mice showed significant increase in the expression levels of anti-oxidative genes and decrease of Nur77 by FGF1∆HBS treatment. Both in vivo and in vitro studies indicate that FGF1∆HBS exerted these beneficial effects by markedly reducing mitochondrial fragmentation, reactive oxygen species (ROS) generation and cytochrome c leakage and enhancing mitochondrial respiration rate and β-oxidation in a 5’ AMP-activated protein kinase (AMPK)/Nur77-dependent manner, all of which were not observed in the AMPK null mice. The favorable metabolic activity and reduced proliferative properties of FGF1∆HBS testify to its promising potential for use in the treatment of DCM and other metabolic disorders.

scholarly journals Isosteviol ameliorates diabetic cardiomyopathy in rats by inhibiting ERK and NF-κB signaling pathways

2018 ◽  
Vol 238 (1) ◽  
pp. 47-60 ◽  
Author(s):  
Sheng-Gao Tang ◽  
Xiao-Yu Liu ◽  
Ji-Ming Ye ◽  
Ting-Ting Hu ◽  
Ying-Ying Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Diabetic Cardiomyopathy ◽  
Nuclear Factor Κb ◽  
Diabetic Rats ◽  
Signal Pathways ◽  
Mortality And Morbidity ◽  
Beneficial Effects ◽  
Male Wistar Rats ◽  
Glucose Plasma

Diabetes-induced injury of myocardium, defined as diabetic cardiomyopathy (DCM), accounts for significant mortality and morbidity in diabetic population. Alleviation of DCM by a potent drug remains considerable interests in experimental and clinical researches because hypoglycemic drugs cannot effectively control this condition. Here, we explored the beneficial effects of isosteviol sodium (STVNa) on type 1 diabetes-induced DCM and the potential mechanisms involved. Male Wistar rats were induced to diabetes by injection of streptozotocin (STZ). One week later, diabetic rats were randomly grouped to receive STVNa (STZ/STVNa) or its vehicle (STZ). After 11 weeks of treatment or 11 weeks treatment following 4 weeks of removal of the treatment, the cardiac function and structure were evaluated and related mechanisms were investigated. In diabetic rats, oxidative stress, inflammation, blood glucose and plasma advanced glycation end products (AGEs) were significantly increased, whereas superoxide dismutase 2 (SOD-2) expression and activity were decreased. STVNa treatment inhibited cardiac hypertrophy, fibrosis and inflammation, showed similar ratio of heart to body weight and antioxidant capacities almost similar to the normal controls, which can be sustained at least 4 weeks. Moreover, STVNa inhibited diabetes-inducted stimulation of both extracellular signal-regulated kinase (ERK) and nuclear factor κB (NF-κB) signal pathways. However, blood glucose, plasma AGE and insulin levels were not altered by STVNa treatment. These results indicate that STVNa may be developed into a potent therapy for DCM. The mechanism underlying this therapeutic effect involves the suppression of oxidative stress and inflammation by inhibiting ERK and NF-κB without changing blood glucose or AGEs.

scholarly journals The Drug Candidate BGP-15 Delays the Onset of Diastolic Dysfunction in the Goto-Kakizaki Rat Model of Diabetic Cardiomyopathy

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 586 ◽  
Author(s):  
Mariann Bombicz ◽  
Daniel Priksz ◽  
Rudolf Gesztelyi ◽  
Rita Kiss ◽  
Nora Hollos ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Animal Studies ◽  
Cardiovascular Effects ◽  
Aortic Ring ◽  
Drug Candidate ◽  
Beneficial Effects ◽  
Healthy Control ◽  
Ring Method ◽  
Vascular Status

Background and Aims: Diabetic cardiomyopathy (DCM) is an emerging problem worldwide due to an increase in the incidence of type 2 diabetes. Animal studies have indicated that metformin and pioglitazone can prevent DCM partly by normalizing insulin resistance, and partly by other, pleiotropic mechanisms. One clinical study has evidenced the insulin-senzitizing effect of the drug candidate BGP-15, along with additional animal studies that have confirmed its beneficial effects in models of diabetes, muscular dystrophy and heart failure, with the drug affecting chaperones, contractile proteins and mitochondria. Our aim was to investigate whether the inzulin-senzitizer BGP-15 exert any additive cardiovascular effects compared to metformin or pioglitazone, using Goto-Kakizaki (GotoK) rats. Methods: Rats were divided into five groups: (I) healthy control (Wistar), (II) diseased (GotoK), and GotoK rats treated with: (III) BGP-15, (IV) metformin, and (V) pioglitazone, respectively, for 12 weeks. Metabolic parameters and insulin levels were determined at the endpoint. Doppler echocardiography was carried out to estimate diabetes-associated cardiac dysfunction. Thoracotomy was performed after the vascular status of rats was evaluated using an isolated aortic ring method. Furthermore, western blot assays were carried out to determine expression or phosphorylation levels of selected proteins that take part in myocyte relaxation. Results: BGP-15 restored diastolic parameters (e′/a′, E/e′, LAP, E and A wave) and improved Tei-index compared to untreated GotoK rats. Vascular status was unaffected by BGP-15. Expression of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) and phosphodiesterase 9A (PDE9A) were unchanged by the treatments, but the phosphorylation level of vasodilator-stimulated phosphoprotein (VASP) and phospholamban (PLB) increased in BGP-15-treated rats, in comparison to GotoK. Conclusions: Even though the BGP-15-treatment did not interfere significantly with glucose homeostasis and vascular status, it considerably enhanced diastolic function, by affecting the SERCA/phospholamban pathway in GotoK rats. Although it requires further investigation, BGP-15 may offer a new therapeutic approach in DCM.

scholarly journals SIRT1 Activation by Resveratrol Alleviates Cardiac Dysfunction via Mitochondrial Regulation in Diabetic Cardiomyopathy Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Sai Ma ◽  
Jing Feng ◽  
Ran Zhang ◽  
Jiangwei Chen ◽  
Dong Han ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Dynamics ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Beneficial Effects ◽  
Mitochondrial Regulation ◽  
And Function

Background. Diabetic cardiomyopathy (DCM) is a major threat for diabetic patients. Silent information regulator 1 (SIRT1) has a regulatory effect on mitochondrial dynamics, which is associated with DCM pathological changes. Our study aims to investigate whether resveratrol, a SRIT1 activator, could exert a protective effect against DCM. Methods and Results. Cardiac-specific SIRT1 knockout (SIRT1KO) mice were generated using Cre-loxP system. SIRT1KO mice displayed symptoms of DCM, including cardiac hypertrophy and dysfunction, insulin resistance, and abnormal glucose metabolism. DCM and SIRT1KO hearts showed impaired mitochondrial biogenesis and function, while SIRT1 activation by resveratrol reversed this in DCM mice. High glucose caused increased apoptosis, impaired mitochondrial biogenesis, and function in cardiomyocytes, which was alleviated by resveratrol. SIRT1 deletion by both SIRT1KO and shRNA abolished the beneficial effects of resveratrol. Furthermore, the function of SIRT1 is mediated via the deacetylation effect on peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), thus inducing increased expression of nuclear respiratory factor 1 (NRF-1), NRF-2, estrogen-related receptor-α (ERR-α), and mitochondrial transcription factor A (TFAM). Conclusions. Cardiac deletion of SIRT1 caused phenotypes resembling DCM. Activation of SIRT1 by resveratrol ameliorated cardiac injuries in DCM through PGC-1α-mediated mitochondrial regulation. Collectively, SIRT1 may serve as a potential therapeutic target for DCM.

scholarly journals Resveratrol and Diabetic Cardiomyopathy: Focusing on the Protective Signaling Mechanisms

2020 ◽  
Vol 2020 ◽  
pp. 1-19 ◽  
Author(s):  
Yan-Jun Song ◽  
Chong-Bin Zhong ◽  
Wei Wu
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Early Stage ◽  
Heart Diseases ◽  
Diabetic Patients ◽  
Beneficial Effects ◽  
Forkhead Box ◽  
Protective Signaling ◽  
Extracellular Regulated Protein Kinases

Diabetic cardiomyopathy (DCM) is a common cardiovascular complication of diabetic mellitus that is characterized by diastolic disorder in the early stage and clinical heart failure in the later stage. Presently, DCM is considered one of the major causes of death in diabetic patients. Resveratrol (RSV), a naturally occurring stilbene, is widely reported as a cardioprotective substance in many heart diseases. Thus far, the specific roles of RSV in DCM prevention and treatment have attracted great attention. Here, we discuss the roles of RSV in DCM by focusing its downstream targets from both in vivo and in vitro studies. Among such targets, Sirtuins 1/3 and AMP-activated kinase have been identified as key mediators that induce cardioprotection during hyperglycemia. In addition, many other signaling molecules (e.g., forkhead box-O3a and extracellular regulated protein kinases) are also regulated in the presence of RSV and exert beneficial effects such as opposing oxidative stress, inflammation, and apoptosis in cardiomyocytes exposed to high-glucose conditions. The beneficial potential of an RSV/stem cell cotherapy is also reviewed as a promising therapeutic strategy for preventing the development of DCM.

scholarly journals SGLT1 Inhibition Attenuates Apoptosis in Diabetic Cardiomyopathy via the JNK and p38 Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Na Lin ◽  
Hui Lin ◽  
Qi Yang ◽  
Wenqiang Lu ◽  
Zhenzhu Sun ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Area Under The Curve ◽  
Underlying Mechanism ◽  
Male Rats ◽  
Diabetic Patients ◽  
Roc Curve Analysis ◽  
Beneficial Effects ◽  
Sodium Glucose Cotransporter ◽  
H9c2 Cardiomyocytes ◽  
P38 Pathway

Background: Recent studies have revealed that a novel selective sodium-glucose cotransporter 1 (SGLT1) inhibiton has shown beneficial effects in cardiovascular diseases. However, the question of whether SGLT1 inhibition influences diabetic cardiomyopathy (DCM) remains unanswered. In this study, we investigated the influence and underlying mechanism of SGLTI inhibition on DCM.Methods: SGLT1 levels were measured in diabetic patients with similar conditions who visited our hospital from January to December 2019. Wistar male rats (n = 50) were divided into five groups: control, diabetes induced by streptozotocin infusion, and diabetes treated with 0.5, 1.0, or 1.5 mg/kg mizagliflozin via stomach gavage for 12 weeks. H9C2 cardiomyocytes were treated with mizagliflozin and then exposed to a high glucose concentration (30 mmol/L). TUNEL assays were performed, and bcl2, bax, p-p38, p-Erk, p-JNK and caspase-3 levels were measured. We used siRNA and an SGLT1 overexpression plasmid to detect the effects of SGLT1.Results: SGLT1 levels were significantly elevated in DCM patients, and receiver operating characteristic (ROC) curve analysis identified SGLT1 as influencing DCM. The area under the curve (AUC) was 0.705 (p < 0.05), with 65.8% sensitivity, and 62.2% specificity. SGLT1 inhibition appeared to attenuate apoptosis in DCM via the JNK and p38 pathway.Conclusion: SGLT1 can be used as a marker for the diagnosis of DCM, and SGLT1 inhibition can attenuate apoptosis, thereby suppressing DCM development via the JNK and p38 pathway.

scholarly journals Resveratrol Modulates Apoptosis and Autophagy Induced by High Glucose and Palmitate in Cardiac Cells

2018 ◽  
Vol 46 (5) ◽  
pp. 2031-2040 ◽  
Author(s):  
Kui Xu ◽  
Xiu-fen Liu ◽  
Zhi-qiang Ke ◽  
Qing Yao ◽  
Shuang Guo ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Apoptotic Cell ◽  
Cardiac Cells ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Important Target ◽  
Downstream Effectors ◽  
Myoblast Cells

Background/Aims: Diabetic cardiomyopathy is associated with increased apoptosis and suppressed autophagy in cardiac cells. The polyphenol resveratrol has shown beneficial effects in various cardiovascular diseases. This study investigated if resveratrol protected cardiac cells by modulating apoptosis and autophagy in the context of diabetes. Methods: H9c2 cardiac myoblast cells were exposed to high glucose combined with palmitate. Autophagy was evaluated by estimating LC3-II/I ratio, P62 protein levels, and LC3 fluorescent puncta. Apoptosis was assessed by using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), flow cytometry, and analysis of the protein expression of apoptotic markers (cleavage of caspase-3 and PARP). Results: High glucose and palmitate suppressed autophagic activity and exacerbated apoptotic cell death in cardiac myoblast cells. Resveratrol restored autophagy and attenuated apoptosis in cells upon diabetic stimuli. Moreover, resveratrol activated AMPK and JNK1, thereby suppressing mTOR and its downstream effectors p70S6K1 and 4EBP1, as well as disrupting the Beclin1–Bcl-2 complex. Conclusion: Resveratrol protects cardiac cells by regulating the switch between autophagy and apoptotic machinery under diabetic conditions, which is attributed by AMPK-mediated phosphorylation of mTORC1/p70S6K1/4EBP1 and JNK-mediated dissociation of Beclin1-Bcl-2. Our study suggests that autophagy may be an important target for resveratrol in the treatment of diabetic cardiomyopathy.

Beneficial Effects of Verapamil in Diabetic Cardiomyopathy

Diabetes ◽  
1988 ◽  
Vol 37 (7) ◽  
pp. 936-942 ◽  
Author(s):  
N. Afzal ◽  
P. K. Ganguly ◽  
K. S. Dhalla ◽  
G. N. Pierce ◽  
P. K. Singal ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Beneficial Effects
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