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 Exercise Training Attenuates Upregulation of p47phoxand p67phoxin Hearts of Diabetic Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Neeru M. Sharma ◽  
Brandon Rabeler ◽  
Hong Zheng ◽  
Eugenia Raichlin ◽  
Kaushik P. Patel
Keyword(s):  
Exercise Training ◽  
Nadph Oxidase ◽  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Cardiac Tissues ◽  
Beneficial Effects ◽  
Collagen Iii

Exercise training (ExT) is currently being used as a nonpharmacological strategy to improve cardiac function in diabetic patients. However, the molecular mechanism(s) underlying its beneficial effects remains poorly understood. Oxidative stress is known to play a key role in the pathogenesis of diabetic cardiomyopathy and one of the enzyme systems that produce reactive oxygen species is NADH/NADPH oxidase. The goal of this study was to investigate the effect of streptozotocin- (STZ-) induced diabetes on expression ofp47phoxandp67phox, key regulatory subunits of NADPH oxidase, in cardiac tissues and determine whether ExT can attenuate these changes. Four weeks after STZ treatment, expression ofp47phoxandp67phoxincreased 2.3-fold and 1.6-fold, respectively, in left ventricles of diabetic rats and these increases were attenuated with three weeks of ExT, initiated 1 week after onset of diabetes. In atrial tissues, there was increased expression ofp47phox(74%), which was decreased by ExT in diabetic rats. Furthermore, increased collagen III levels in diabetic hearts (52%) were significantly reduced by ExT. Taken together, ExT attenuates the increased expression ofp47phoxandp67phoxin the hearts of diabetic rats which could be an underlying mechanism for improving intracardiac matrix and thus cardiac function and prevent cardiac remodeling in diabetic cardiomyopathy.

scholarly journals Quetiapine Attenuates the Neuroinflammation and Executive Function Deficit in Streptozotocin-Induced Diabetic Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Kexin Wang ◽  
Feng Song ◽  
Hongxing Wang ◽  
Jun-hui Wang ◽  
Yu Sun
Keyword(s):  
Cognitive Deficit ◽  
Neuroprotective Effect ◽  
Underlying Mechanism ◽  
Diabetic Mouse ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Protein Loss ◽  
Monocyte Chemoattractant Protein 1 ◽  
Beneficial Effects ◽  
Increased Risk

Diabetic patients are at increased risk for developing memory and cognitive deficit. Prior studies indicate that neuroinflammation might be one important underlying mechanism responsible for this deficit. Quetiapine (QTP) reportedly exerts a significant neuroprotective effect in animal and human studies. Here, we investigated whether QTP could prevent memory deterioration and cognitive impairment in a streptozotocin- (STZ-) induced diabetic mouse model. In this study, we found that STZ significantly compromised the behavioral performance of mice in a puzzle box test, but administering QTP effectively attenuated this behavioral deficit. Moreover, our results showed that QTP could significantly inhibit the activation of astrocytes and microglia in these diabetic mice and reduce the generation and release of two cytokines, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). Meanwhile, QTP also prevented the protein loss of the synaptic protein synaptophysin (SYP) and myelin basic protein (MBP). Here, our results indicate that QTP could inhibit neuroinflammatory response from glial cells and block the injury of released cytokines to neurons and oligodendrocytes in diabetic mice (DM). These beneficial effects could protect diabetic mice from the memory and cognitive deficit. QTP may be a potential treatment compound to handle the memory and cognitive dysfunction in diabetic patients.

scholarly journals Comparison of the usefulness of plasma levels of oxidatively modified forms of albumin in estimating kidney dysfunction in diabetic patients

2010 ◽  
Vol 33 (2) ◽  
pp. 109 ◽  
Author(s):  
Agnieszka Piwowar ◽  
Maria Knapik-Kordecka ◽  
Maria Warwas
Keyword(s):  
Oxidative Stress ◽  
Plasma Levels ◽  
Area Under The Curve ◽  
Diabetic Patients ◽  
Clinical Markers ◽  
Kidney Dysfunction ◽  
Roc Curve Analysis ◽  
Type 2 Diabetic Patients ◽  
Oxidatively Modified ◽  
Two Parameters

Purpose: Advanced oxidation protein products (AOPP) and ischemia-modified albumin (IMA) are forms of oxidatidatively modified albumin and have recently been investigated as indicators of oxidative stress. They are increased in different disorders, including diabetes mellitus, as a result of hyperglycaemia, oxidative stress and hypoxia. The usefulness of the plasma levels of these two parameters in estimating kidney dysfunction in type 2 diabetic patients (T2DM) was compared in this study. Methods: Plasma levels of AOPP and IMA were determined spectrophotometrically in 218 individuals, 153 patients with T2DM and 65 healthy people.. The urinary albumin/creatinine ratio (UACR) was used as the reference to define the stage of kidney dysfunction by the assessment of the degree of albuminuria. Results: Receiver Operating Characteristic (ROC) curve analysis, likelihood ratio (LR), and Youden’s index (J) revealed that AOPP and IMA had acceptable sensitivities and specificities in individuals with different degrees of albuminuria; however, AOPP had higher values of the area under the curve (AUC: 0.934) than IMA, as well as 100% sensitivity and 77.01% specificity for distinguishing patients with micro- and macroalbuminuria. Conclusions: Both AOPP and IMA may be helpful clinical markers for estimating kidney dysfunction, but AOPP is better able to identify diabetic patients with nephropathy. We suggest that AOPP is almost ideal for discriminating between T2DM patients with micro- and macroalbuminuria.

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.

Effect of sodium-glucose cotransporter-2 inhibitors on renal handling of electrolytes

2021 ◽  
pp. postgradmedj-2020-139348
Author(s):  
Priti Meena ◽  
Vinant Bhargava ◽  
Anil Bhalla ◽  
Devinder Rana ◽  
Alok Mantri
Keyword(s):  
Serum Levels ◽  
Underlying Mechanism ◽  
Renal Handling ◽  
Beneficial Effects ◽  
Electrolyte Disturbances ◽  
Sodium Glucose Cotransporter ◽  
Pressure Lowering ◽  
Present Decade ◽  
Cardioprotective Effects ◽  
Putative Mechanism

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are the latest introduction into the armamentarium of diabetes care in the present decade. By virtue of their beneficial effects, such as blood pressure-lowering, bodyweight reduction and significant renal and cardioprotective effects which extends beyond their glycaemic control effects, SGLT2i have become one of the most preferred oral antihyperglycaemic agents of recent times. However, they can influence tubular handling of electrolytes that can result in some electrolyte disturbances such as alteration in the serum levels of magnesium, potassium and phosphate levels. Some of these changes are mild or transient and may not have significant clinical implications. The underlying putative mechanism(s) responsible for disturbances of electrolytes are yet to be deciphered. In this review, we aim to describe electrolytes and acid–base abnormalities due to SGLT2i as well as to elucidate the underlying mechanism.

scholarly journals 3,5 Diiodo-l-Thyronine (T2) Promotes the Browning of White Adipose Tissue in High-Fat Diet-Induced Overweight Male Rats Housed at Thermoneutrality

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 256 ◽  
Author(s):  
Rosalba Senese ◽  
Federica Cioffi ◽  
Rita De Matteis ◽  
Giuseppe Petito ◽  
Pieter de Lange ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fat Mass ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Underlying Mechanism ◽  
Male Rats ◽  
Standard Diet ◽  
High Fat ◽  
Beneficial Effects ◽  
Adipose Cells

The conversion of white adipose cells into beige adipose cells is known as browning, a process affecting energy metabolism. It has been shown that 3,5 diiodo-l-thyronine (T2), an endogenous metabolite of thyroid hormones, stimulates energy expenditure and a reduction in fat mass. In light of the above, the purpose of this study was to test whether in an animal model of fat accumulation, T2 has the potential to activate a browning process and to explore the underlying mechanism. Three groups of rats were used: (i) receiving a standard diet for 14 weeks; (ii) receiving a high-fat diet (HFD) for 14 weeks; and (iii) receiving a high fat diet for 10 weeks and being subsequently treated for four weeks with an HFD together with the administration of T2. We showed that T2 was able to induce a browning in the white adipose tissue of T2-treated rats. We also showed that some miRNA (miR133a and miR196a) and MAP kinase 6 were involved in this process. These results indicate that, among others, the browning may be another cellular/molecular mechanism by which T2 exerts its beneficial effects of contrast to overweight and of reduction of fat mass in rats subjected to HFD.

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

Dietary Quercetin Alleviated DSS-induced Colitis in Mice Through Several Possible Pathways by Transcriptome Analysis

2020 ◽  
Vol 21 (15) ◽  
pp. 1666-1673 ◽  
Author(s):  
Yuanyang Dong ◽  
Jiaqi Lei ◽  
Bingkun Zhang
Keyword(s):  
Antioxidant Capacity ◽  
Underlying Mechanism ◽  
Control Group ◽  
Sequencing Analysis ◽  
Colon Tissue ◽  
Beneficial Effects ◽  
Intestinal Integrity ◽  
Inflammatory Bowel ◽  
Vegetables And Fruits ◽  
Key Pathways

Background: The prevalence of inflammatory bowel disease is rapidly increasing around the world. Quercetin is a flavonoid commonly found in vegetables and fruits and has been reported to exert numerous pharmacological activities such as enhancing antioxidant capacity or suppressing inflammation. Objective: We aimed to explore whether quercetin was effective for IBD and the underlying mechanism of quercetin for the ameliorative effects on the DSS-induced colitis in mice. Methods: Thirty-six mice were randomly assigned to three treatments, including the control group (Ctr), DSS-induced colitis group (DSS) and DSS-induced colitis supplemented with 500 ppm quercetin (DQ500). Colitis was induced by DSS intake, and body weight was recorded every day. After six days administration of DSS, intestinal permeability was measured, and the liver was taken for antioxidant enzyme tests. Colonic tissue was taken for the histopathlogical score and RNA-sequencing analysis. Results: In this experiment, dietary quercetin for 500ppm alleviated the DSS-induced colitis, possibly by strengthening intestinal integrity, liver antioxidant capacity. Based on the results of the transcriptome of colon tissue, several key genes were modulated by quercetin. ERK1/2-FKBP pathway and RXR-STAT3 pathway were involved in the development of IBD, furthermore, in the down-regulation of S100a8/9, FBN2 contributed to lowering the risk of colongenesis. Conclusion: We demonstrated that dietary quercetin alleviated the DSS-induced colitis in mice. This is most likely due to its beneficial effects on intestinal integrity and modulation of several key pathways. Based on our research, quercetin was a promising candidate for IBD and its pharmaceutical effects on both IBD and colongenesis need further research.

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