Exenatide inhibits NF-κB and attenuates ER stress in diabetic cardiomyocyte models

Fu, Zhenhong; Mui, David; Zhu, Hang; Zhang, Ying

doi:10.18632/aging.103181

Cited by 21 publications

(14 citation statements)

References 68 publications

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“…Cardiomyocyte/cardiac fibroblast dysfunction is related to abnormal proliferation, apoptosis, hypertrophy, as well as inflammation and fibrosis, which may be caused by mitochondrial dysfunction and metabolic disorders. Persistent hyperglycemia can mediate hypoxic or ischemic injury, as well as elicit cardiomyocyte contractile dysfunction and the NF-κB signaling pathway activation, thus inducing ER stress [152]. GLP-1RA can help maintain a balance of energy metabolism in cardiomyocytes through activating PI3K/Akt as well as p38 MAPK pathways as well as activating Nrf-2/heme oxygenase-1 (HO-1), contributing to augmented adenosine triphosphate formation and glucose ingestion by cardiomyocytes [153][154][155].…”

Section: Improving Cardiomyocyte/cardiac Fibroblast Dysfunction By Glp-1rasmentioning

confidence: 99%

“…Hyperglycemia-mediated cardiomyocyte damage is associated with inflammation. GLP-1RAs can have effects on inflammation and defending ER stress via suppressing NF-κB in diabetic cardiomyocyte models [152]. GLP-1R can also suppress cardiac hypertrophy induced by Ang II through attenuating the Nox4-histone deacetylase 4 (HDAC4) axis [162].…”

Section: Improving Cardiomyocyte/cardiac Fibroblast Dysfunction By Glp-1rasmentioning

confidence: 99%

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GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential

Ma¹,

Liu²,

Ilyas³

et al. 2021

Int. J. Biol. Sci.

121

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Type 2 diabetes mellitus (T2DM) is closely associated with cardiovascular diseases (CVD), including atherosclerosis, hypertension and heart failure. Some anti-diabetic medications are linked with an increased risk of weight gain or hypoglycemia which may reduce the efficacy of the intended anti-hyperglycemic effects of these therapies. The recently developed receptor agonists for glucagon-like peptide-1 (GLP-1RAs), stimulate insulin secretion and reduce glycated hemoglobin levels without having side effects such as weight gain and hypoglycemia. In addition, GLP1-RAs demonstrate numerous cardiovascular protective effects in subjects with or without diabetes. There have been several cardiovascular outcomes trials (CVOTs) involving GLP-1RAs, which have supported the overall cardiovascular benefits of these drugs. GLP1-RAs lower plasma lipid levels and lower blood pressure (BP), both of which contribute to a reduction of atherosclerosis and reduced CVD. GLP-1R is expressed in multiple cardiovascular cell types such as monocyte/macrophages, smooth muscle cells, endothelial cells, and cardiomyocytes. Recent studies have indicated that the protective properties against endothelial dysfunction, anti-inflammatory effects on macrophages and the anti-proliferative action on smooth muscle cells may contribute to atheroprotection through GLP-1R signaling. In the present review, we describe the cardiovascular effects and underlying molecular mechanisms of action of GLP-1RAs in CVOTs, animal models and cultured cells, and address how these findings have transformed our understanding of the pharmacotherapy of T2DM and the prevention of CVD.

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Section: Improving Cardiomyocyte/cardiac Fibroblast Dysfunction By Glp-1rasmentioning

confidence: 99%

Section: Improving Cardiomyocyte/cardiac Fibroblast Dysfunction By Glp-1rasmentioning

confidence: 99%

GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential

Ma¹,

Liu²,

Ilyas³

et al. 2021

Int. J. Biol. Sci.

121

View full text Add to dashboard Cite

show abstract

“…Previous studies found that depression might play a role in the pathogenesis of DM in some ways: i) some environmental stressors resulted in depression and simultaneously influenced the glucose metabolism [ 31 , 32 ]; ii) depression could be an independent factor in influencing the nutrition and lifestyle behaviors of patients [ 31 , 32 ]; iii) depression had a close relationship with the disturbed gut microbiota, and the stable gut microbiota was also important to the health of patients with DM [ 33 – 35 ]; iv) depression could lead to the over-activation of hypothalamic-pituitary-adrenal (HPA) axis and inflammatory response to stress [ 36 , 37 ]; and the inflammation had an important role in the onset of DM [ 38 – 41 ]. Here, we found that these antidepressants could significantly reduce the HDRS score and HbA1c level in depressed T2DM patients.…”

Section: Discussionmentioning

confidence: 99%

Agomelatine might be more appropriate for elderly, depressed, type 2 diabetes mellitus patients than paroxetine/fluoxetine

Liang

Jia

Zhao

et al. 2021

Aging

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Agomelatine was a novel and melatonergic antidepressant. The present study was conducted to find out whether age was an important factor for agomelatine in treating depressed type 2 diabetes mellitus (T2DM) patients. In total, 193 depressed T2DM patients were included. There were 84 patients ranged from 27 years old to 49 years old (age phase I) ( n = 44 receiving agomelatine, n = 40 receiving paroxetine or fluoxetine), and 109 patients ranged from 50 years old to 70 years old (age phase II) ( n = 56 receiving agomelatine, n = 53 receiving paroxetine or fluoxetine). The Hamilton Depression Rating Scale (HDRS) score, Hamilton Anxiety Rating Scale (HARS) score, fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) level and body mass index (BMI) were assessed after 12 weeks treatment. After treatment, we found that among patients in age phase I, there were no significant differences in final average HDRS score, HARS score, FPG, HbA1c level, BMI, response rate and remission rate between the two groups. However, among patients in age phase II, compared to patients receiving paroxetine or fluoxetine, patients receiving agomelatine had the significantly lower average HDRS score, HARS score, HbA1c level and BMI, and significantly higher response rate and remission rate. The incidence of treatment-related adverse events was similar between the two groups in both age phases. These results suggested that age was an important factor for agomelatine in treating depressed T2DM patients. Compared to paroxetine/fluoxetine, agomelatine might be more appropriate for elderly depressed T2DM patients.

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“…In particular, the following mechanisms are activated: (1) nargirin activates glutathione (GSH), ensuring a new antioxidant defense mechanism; (2) naringin prevents the progression of hyperglycemia by increasing hepatic glycolysis and lowering hepatic gluconeogenesis; (3) nargirin shows antidiabetic effects; (4) naringin inhibits the hyperglycemia-induced NF-κB pathway [ 156 ]. The involvement of SR stress in diabetic cardiomyopathy was also demonstrated by the important results obtained in an in vitro study on H9c2 embryonic rat cardiomyoblast maintained in culture and exposed to high glucose concentrations [ 172 ]. In this study, when the cells were exposed to exenatide, a drug used in the treatment of Type 2 diabetes mellitus, the inhibition of the NF-κB signaling pathway was observed, reducing SR stress induced by hyperglycemia [ 162 ].…”

Section: Diabetic Cardiomyopathy and Bergamot Polyphenolsmentioning

confidence: 99%

Effects of Bergamot Polyphenols on Mitochondrial Dysfunction and Sarcoplasmic Reticulum Stress in Diabetic Cardiomyopathy

et al. 2021

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Cardiovascular disease is the leading cause of death and disability in the Western world. In order to safeguard the structure and the functionality of the myocardium, it is extremely important to adequately support the cardiomyocytes. Two cellular organelles of cardiomyocytes are essential for cell survival and to ensure proper functioning of the myocardium: mitochondria and the sarcoplasmic reticulum. Mitochondria are responsible for the energy metabolism of the myocardium, and regulate the processes that can lead to cell death. The sarcoplasmic reticulum preserves the physiological concentration of the calcium ion, and triggers processes to protect the structural and functional integrity of the proteins. The alterations of these organelles can damage myocardial functioning. A proper nutritional balance regarding the intake of macronutrients and micronutrients leads to a significant improvement in the symptoms and consequences of heart disease. In particular, the Mediterranean diet, characterized by a high consumption of plant-based foods, small quantities of red meat, and high quantities of olive oil, reduces and improves the pathological condition of patients with heart failure. In addition, nutritional support and nutraceutical supplementation in patients who develop heart failure can contribute to the protection of the failing myocardium. Since polyphenols have numerous beneficial properties, including anti-inflammatory and antioxidant properties, this review gathers what is known about the beneficial effects of polyphenol-rich bergamot fruit on the cardiovascular system. In particular, the role of bergamot polyphenols in mitochondrial and sarcoplasmic dysfunctions in diabetic cardiomyopathy is reported.

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Exenatide inhibits NF-κB and attenuates ER stress in diabetic cardiomyocyte models

Cited by 21 publications

References 68 publications

GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential

GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential

Agomelatine might be more appropriate for elderly, depressed, type 2 diabetes mellitus patients than paroxetine/fluoxetine

Effects of Bergamot Polyphenols on Mitochondrial Dysfunction and Sarcoplasmic Reticulum Stress in Diabetic Cardiomyopathy

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