Metabolic remodelling in diabetic cardiomyopathy

AbstractDiabetes is a risk factor for heart failure and cardiovascular mortality with specific changes to myocardial metabolism, energetics, structure, and function. The gradual impairment of insulin production and signalling in diabetes is associated with elevated plasma fatty acids and increased myocardial free fatty acid uptake and activation of the transcription factor PPARα. The increased free fatty acid uptake results in accumulation of toxic metabolites, such as ceramide and diacylglycerol, activation of protein kinase C, and elevation of uncoupling protein-3. Insulin signalling and glucose uptake/oxidation become further impaired, and mitochondrial function and ATP production become compromised. Increased oxidative stress also impairs mitochondrial function and disrupts metabolic pathways. The diabetic heart relies on free fatty acids (FFA) as the major substrate for oxidative phosphorylation and is unable to increase glucose oxidation during ischaemia or hypoxia, thereby increasing myocardial injury, especially in ageing female diabetic animals. Pharmacological activation of PPARγ in adipose tissue may lower plasma FFA and improve recovery from myocardial ischaemic injury in diabetes. Not only is the diabetic heart energetically-impaired, it also has early diastolic dysfunction and concentric remodelling. The contractile function of the diabetic myocardium negatively correlates with epicardial adipose tissue, which secretes proinflammatory cytokines, resu...
Source: Cardiovascular Research - Category: Cardiology Source Type: research

Related Links:

ConclusionOur work confirms that the Akita mouse model of diabetes replicates key clinical features of diabetic HFpEF, including cardiac and mitochondrial dysfunction. Furthermore, in this independent study, MitoGamide treatment improved diastolic function in Akita mice.
Source: Cardiovascular Drugs and Therapy - Category: Cardiology Source Type: research
Abstract Type 2 diabetes (T2D) substantially elevates the risk for heart failure, a major cause of death. In advanced T2D, energy metabolism in the heart is disrupted; glucose metabolism is decreased, fatty acid (FA) metabolism is enhanced to maintain ATP production, and cardiac function is impaired. This condition is termed diabetic cardiomyopathy (DCM). The exact cause of DCM is still unknown although altered metabolism is an important component. While type 2 diabetes is characterized by insulin resistance, the traditional antidiabetic agents that improve insulin stimulation or sensitivity only partially improve...
Source: Current Opinion in Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Opin Pharmacol Source Type: research
AbstractATTR amyloidosis is caused by systemic deposition of transthyretin (TTR) and comprises ATTRwt (wt for wild-type) amyloidosis, ATTRv (v for variant) amyloidosis, and acquired ATTR amyloidosis after domino liver transplantation. ATTRwt amyloidosis has classically been regarded as cardiomyopathy found in the elderly, whereas carpal tunnel syndrome has also become a major initial manifestation. The phenotypes of ATTRv amyloidosis are diverse and include neuropathy, cardiomyopathy, and oculoleptomeningeal involvement as the predominant features, depending on the mutation and age of onset. In addition to variant TTR, the...
Source: Neurology and Therapy - Category: Neurology Source Type: research
As the most metabolically demanding organ in the body, the heart must generate massive amounts of energy adenosine triphosphate (ATP) from the oxidation of fatty acids, carbohydrates and other fuels (e.g., amino acids, ketone bodies), in order to sustain constant contractile function. While the healthy mature heart acts omnivorously and is highly flexible in its ability to utilize the numerous fuel sources delivered to it through its coronary circulation, the heart’s ability to produce ATP from these fuel sources becomes perturbed in numerous cardiovascular disorders. This includes ischemic heart disease and myocardi...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
BRD4 is a member of the BET family of epigenetic regulators. Inhibition of BRD4 by the selective bromodomain inhibitor JQ1, alleviates thoracic aortic constriction-induced cardiac hypertrophy and heart failure. However, whether BRD4 inhibition by JQ1 has therapeutic effect on diabetic cardiomyopathy, a major cause of heart failure in patients with Type 2 diabetes, remains unknown. Here, we discover a novel link between BRD4 and PINK1/Parkin-mediated mitophagy during diabetic cardiomyopathy. Upregulation of BRD4 in diabetic mouse hearts inhibits PINK1/Parkin-mediated mitophagy, resulting in accumulation of damaged mitochond...
Source: Journal of Molecular and Cellular Cardiology - Category: Cytology Authors: Source Type: research
AbstractTrabeculation exhibits highly varied presentations, whereas noncompaction (NC) is a specific disease entity based arithmetically on wall thickness. We aimed to evaluate the clinical implications of trabeculation and its relevance to outcomes. A total of 296 patients (age 63  ± 12 years; 64% men) with trabeculation who underwent echocardiography were retrospectively identified between January 2011 and December 2012. Analyses were conducted on distinguished trabeculation which was divided into NC (maximum noncompacted/compacted ratio ≥ 2.0) or hypertrabeculat ion (HT) (ratio 
Source: The International Journal of Cardiovascular Imaging - Category: Radiology Source Type: research
Tei index – Myocardial performance index Tei index – myocardial performance index (MPI) is the ratio of the time spent in isovolumetric activity divided by the time spent in ventricular ejection [1]. In other words, it is the sum of isovolumic contraction and relaxation times divided by the ejection time [2]. MPI = (ICT + IRT) / ET ICT: isovolumic contraction time; IRT: isovolumic relaxation time; ET: ejection time Myocardial performance index has an inverse relation with global ventricular function in that increasing values indicate worsening global ventricular function. There is good correlation between Doppl...
Source: Cardiophile MD - Category: Cardiology Authors: Tags: Echocardiography Source Type: blogs
Abstract Diabetic cardiomyopathy, clinically diagnosed as ventricular dysfunction in the absence of coronary atherosclerosis or hypertension in diabetic patients, is a cardiac muscle-specific disease that increases the risk of heart failure and mortality. Its clinical course is characterized initially by diastolic dysfunction, later by systolic dysfunction, and eventually by clinical heart failure from an uncertain mechanism. Light microscopic features such as interstitial fibrosis, inflammation, and cardiomyocyte hypertrophy are observed in diabetic cardiomyopathy, but are common to failing hearts generally and a...
Source: Journal of Cardiology - Category: Cardiology Authors: Tags: J Cardiol Source Type: research
AbstractIntroductionsDiabetic cardiomyopathy is a type of myocardial disease. It causes left ventricular hypertrophy, followed by diastolic and systolic dysfunction, eventually leading to congestive heart failure. However, the underlying mechanism still requires further elucidation.Materials and MethodsHigh glucose zebrafish model was constructed by administrating streptozocin intraperitoneally to enhance the development of cardiomyopathy, and then treated with AMPK activator. Cardiac structure and function, protein and gene expression were then analyzed. Cardiomyocytes culture in vitro using lentivirus were used for detec...
Source: Journal of Diabetes Investigation - Category: Endocrinology Authors: Tags: ORIGINAL ARTICLE Source Type: research
Abstract Biomarkers are increasingly recognized to have significant clinical value in early identification and progression of various cardiovascular diseases. There are many heart conditions such as Congestive heart failure (CHF), ischemic heart diseases (IHD), and diabetic cardiomyopathy (DCM) and cardiac remodeling in which the severity of the cardiac pathology can be mirrored through these biomarker or cardiac biomarkers. From the emergency department (ED) evaluation of acute coronary syndromes (ACS) or suspected acute myocardial infarction (AMI) with cardiac marker Troponin to the diagnosis of chronic conditio...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - Category: Endocrinology Authors: Tags: Endocr Metab Immune Disord Drug Targets Source Type: research
More News: Cardiology | Cardiomyopathy | Cardiovascular | Diabetes | Endocrinology | Heart | Heart Failure | Insulin | SGLT2 Inhibitors | Toxicology