Stimulation of GLP-1 Receptor Inhibits Methylglyoxal-Induced Mitochondrial Dysfunctions in H9c2 Cardiomyoblasts: Potential Role of Epac/PI3K/Akt Pathway

Accumulation of methylglyoxal (MG) contributes to oxidative stress, apoptosis, and mitochondrial dysfunction, leading to the development of type 2 diabetes and cardiovascular diseases. Inhibition of mitochondrial abnormalities induced by MG in the heart may improve and delay the progression of heart failure. Although glucagon-like peptide-1 receptor (GLP-1R) agonists have been used as anti-diabetic drugs and GLP-1R has been detected in the heart, the cardioprotective effects of GLP-1R agonists on the inhibition of MG-induced oxidative stress and mitochondrial abnormalities have not been elucidated. Stimulation of GLP-1Rs leads to cAMP elevation and subsequently activates PKA- and/or Epac-dependent signaling pathway. However, the signaling pathway involved in the prevention of MG-induced mitochondrial dysfunctions in the heart has not been clarified so far. In the present study, we demonstrated that stimulation of GLP-1Rs with exendin-4 inhibited MG-induced intracellular and mitochondrial reactive oxygen species (ROS) production and apoptosis in H9c2 cardiomyoblasts. GLP-1R stimulation also improved the alterations of mitochondrial membrane potential (MMP) and expressions of genes related to mitochondrial functions and dynamics induced by MG. In addition, stimulation of GLP-1R exhibits antioxidant and antiapoptotic effects as well as the improvement of mitochondrial functions through cAMP/Epac/PI3K/Akt signaling pathway in H9c2 cells. Our study is the first work demonstrating ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
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Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
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res E Abstract Ischemic heart disease is the main cause of death globally. In the heart, the ischemia/reperfusion injury gives rise to a complex cascade of molecular signals, called cardiac remodeling, which generates harmful consequences for the contractile function of the myocardium and consequently heart failure. Metformin is the drug of choice in the treatment of type 2 diabetes mellitus. Clinical data suggest the direct effects of this drug on cardiac metabolism and studies in animal models showed that metformin activates the classical pathway of AMP-activated protein kinase (AMPK), generating cardioprotectiv...
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
Abstract Sodium-glucose cotransporter 2 inhibitors reduce the risk of serious heart failure and adverse renal events, but the mechanisms that underlie this benefit are not understood. Treatment with SGLT2 inhibitors is distinguished by two intriguing features - ketogenesis and erythrocytosis. Both reflect the induction of a fasting-like and hypoxia-like transcriptional paradigm that is capable of restoring and maintaining cellular homeostasis and survival. In the face of perceived nutrient and oxygen deprivation, cells activate low-energy sensors, which include sirtuin-1 (SIRT1), adenosine monophosphate-activated ...
Source: Circulation - Category: Cardiology Authors: Tags: Circulation Source Type: research
Conclusion A great deal of progress is being made in the matter of treating aging: in advocacy, in funding, in the research and development. It can never be enough, and it can never be fast enough, given the enormous cost in suffering and lost lives. The longevity industry is really only just getting started in the grand scheme of things: it looks vast to those of us who followed the slow, halting progress in aging research that was the state of things a decade or two ago. But it is still tiny compared to the rest of the medical industry, and it remains the case that there is a great deal of work yet to be done at all...
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Conclusion A great deal of progress is being made in the matter of treating aging: in advocacy, in funding, in the research and development. It can never be enough, and it can never be fast enough, given the enormous cost in suffering and lost lives. The longevity industry is really only just getting started in the grand scheme of things: it looks vast to those of us who followed the slow, halting progress in aging research that was the state of things a decade or two ago. But it is still tiny compared to the rest of the medical industry, and it remains the case that there is a great deal of work yet to be done at all...
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Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
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In conclusion, T2D impairs vascular function by dysregulated autophagy. Therefore, autophagy could be a potential target for overcoming diabetic microvascular complications. To What Degree Does Loss of Skeletal Muscle with Age Contribute to Immunosenescence? https://www.fightaging.org/archives/2019/11/to-what-degree-does-loss-of-skeletal-muscle-with-age-contribute-to-immunosenescence/ Sarcopenia, the progressive loss of muscle mass and strength, is characteristic of aging. A perhaps surprisingly large fraction of the losses can be averted by strength training, but there are nonetheless inexorable process...
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