A novel oral glucagon-like peptide 1 receptor agonist protects against diabetic cardiomyopathy via alleviating cardiac lipotoxicity induced mitochondria dysfunction

Pan, Qian; Tian, Hong; Wang, Yongkang; Lu, Weisheng; Li, Ying; Ma, Teng; Gao, Xiangdong; Yao, Wenbing

doi:10.1016/j.bcp.2020.114209

Cited by 24 publications

(20 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies revealed that GLP-1RAs relieve myocardial damage and glucose toxicity by promoting autophagy, which is associated with decreasing mTOR phosphorylation and increasing AMPK phosphorylation [88]. Furthermore, a new orally bioavailable GLP-1RA, oral hypoglycemic peptide 2 (OHP2), can confer protective effects on diabetic cardiomyopathy through rescuing cardiac lipotoxicity by inhibiting Rho (the small GTPase) kinase (ROCK)/PPARα pathway [89,90] (Figure 1).…”

Section: Effects Of Glp-1ras On Cardiomyopathymentioning

confidence: 99%

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

Ma¹,

Liu²,

Ilyas³

et al. 2021

Int. J. Biol. Sci.

135

View full text Add to dashboard Cite

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.

show abstract

Section: Effects Of Glp-1ras On Cardiomyopathymentioning

confidence: 99%

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

Ma¹,

Liu²,

Ilyas³

et al. 2021

Int. J. Biol. Sci.

135

View full text Add to dashboard Cite

show abstract

“…Both hyperlipidemia and myocardium lipid accumulation were decreased by OHP2 treatment. In addition, OHP2 reversed oxidative stress and mitochondrial dysfunction in diabetic hearts ( 284 ).…”

Section: Effects Of Anti-hyperglycemic Drug Therapy On Heart Failure In Diabetesmentioning

confidence: 99%

The Diabetic Cardiomyopathy: The Contributing Pathophysiological Mechanisms

et al. 2021

View full text Add to dashboard Cite

Individuals with diabetes mellitus (DM) disclose a higher incidence and a poorer prognosis of heart failure (HF) than non-diabetic people, even in the absence of other HF risk factors. The adverse impact of diabetes on HF likely reflects an underlying “diabetic cardiomyopathy” (DM–CMP), which may by exacerbated by left ventricular hypertrophy and coronary artery disease (CAD). The pathogenesis of DM-CMP has been a hot topic of research since its first description and is still under active investigation, as a complex interplay among multiple mechanisms may play a role at systemic, myocardial, and cellular/molecular levels. Among these, metabolic abnormalities such as lipotoxicity and glucotoxicity, mitochondrial damage and dysfunction, oxidative stress, abnormal calcium signaling, inflammation, epigenetic factors, and others. These disturbances predispose the diabetic heart to extracellular remodeling and hypertrophy, thus leading to left ventricular diastolic and systolic dysfunction. This Review aims to outline the major pathophysiological changes and the underlying mechanisms leading to myocardial remodeling and cardiac functional derangement in DM-CMP.

show abstract

“…The pathophysiological mechanism of DCM is quite complex, including cardiac interstitial and peripheral vascular fibrosis, autophagy and apoptosis of cardiomyocytes caused by abnormal energy metabolism, oxidative stress and inflammation of cardiomyocytes, and mitochondrial damage 25 . The latest research shows that hypoglycaemic drugs, such as glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase 4 inhibitors, can reduce major adverse cardiovascular events and/or death rates from cardiovascular diseases in patients with type 2 diabetes 26,27 . However, many clinical trials have also shown that glucagon‐like peptide‐1 receptor agonist has not exhibited significant beneficial effects against impaired ventricular function, and the efficacy of dipeptidyl peptidase 4 for different patients is not consistent 28 .…”

Section: Discussionmentioning

confidence: 99%

“…25 The latest research shows that hypoglycaemic drugs, such as glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors, can reduce major adverse cardiovascular events and/or death rates from cardiovascular diseases in patients with type 2 diabetes. 26,27 However, many clinical trials have also shown that glucagon-like peptide-1 receptor agonist has not exhibited significant beneficial effects against impaired ventricular F I G U R E 3 Salidroside prevented diabetes-induced inflammation in rat hearts. PCR analysis of myocardial TNF-α (a), Il-1β (b), Il-6 (c) and MCP-1(d) mRNA in rats with diabetes.…”

Section: Discussionmentioning

confidence: 99%

Salidroside attenuates cardiac dysfunction in a rat model of diabetes

Hao

et al. 2021

Diabet Med

View full text Add to dashboard Cite

Physiological damages directly or indirectly caused by diabetes have become one of the major risks for morbidity and mortality among patients worldwide. 1 Diabetic complications include diabetic cardiovascular diseases, 2 cerebrovascular diseases, kidney diseases, neuropathy, eye diseases and diabetic foot, among which diabetic heart insufficiency is the most deadly. 3 More than 70% of diabetic patients die of cardiovascular diseases, 2-4 times higher than non-diabetic patients. 4,5 The pathophysiological mechanisms of diabetic heart diseases are complicated and mainly include metabolic alterations in the substrate, microvascular dysfunction, renin-angiotensin-aldosterone system activation, oxidative stress, mitochondrial dysfunction, and damaged Ca 2+ transportation, which ultimately leads to coronary artery disease, cardiac failure or even sudden death. 6 Glucotoxicity caused by glucose overload is also the main cause of diabetic cardiac dysfunction. 7 Cardiomyocyte glucose overload caused by impaired glucose metabolism promotes oxidative stress and glycosylation, as well as the chronic activation of hexosamine and other pathways. 8 Cardiomyocyte apoptosis thus activates the mTOR signalling pathway and leads to endoplasmic reticulum (ER) stress, which ultimately causes diabetes-induced

show abstract

A novel oral glucagon-like peptide 1 receptor agonist protects against diabetic cardiomyopathy via alleviating cardiac lipotoxicity induced mitochondria dysfunction

Cited by 24 publications

References 45 publications

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

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

The Diabetic Cardiomyopathy: The Contributing Pathophysiological Mechanisms

Salidroside attenuates cardiac dysfunction in a rat model of diabetes

Contact Info

Product

Resources

About