Articles de revues : « Sodium current, insulin secretion, myocardium »

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Payudis, A. N., O. A. Efremova, L. A. Kamyshnikova, Iu S. Pavlova, O. V. Dudchenko, I. I. Khamnagadaev et T. P. Golivets. « Effect of SGLT2 inhibitors on the course of chronic heart failure in patients with type 2 diabetes mellitus ». Clinician 16, n^o 2 (10 octobre 2022) : 10–16. http://dx.doi.org/10.17650/1818-8338-2022-16-2-k656.

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Diabetes mellitus (DM) is a group of metabolic diseases characterized by chronic hyperglycemia, which is the result of impaired insulin secretion, insulin action, or both. Chronic hyperglycemia in diabetes is accompanied by damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels. Diabetes mellitus plays a significant role in the formation and is one of the significant risk factors for the development of chronic heart failure (CHF) through its glucose toxic effect, the effect on hyperlipidemia and blood coagulation, impaired autonomic regulation of the heart and a number of other mechanisms. Sodium-glucose cotransporter type 2 (SGLT2) inhibitors are a recently emerging class of antidiabetic drugs that act by inhibiting the reabsorption of glucose in the kidneys. Existing studies of the efficacy and safety of these drugs have shown that they have not only antidiabetic, but also a pronounced organoprotective, especially cardioprotective effect. Today it is believed that the main reason leading to this lies in a decrease in sodium reabsorption in the kidneys, a decrease in the content of intracellular calcium and sodium, and an increase in the concentration of calcium in mitochondria. The role of the ketogenic action of these drugs, their effect on oxidative stress and the processes of inflammation and fibrosis in the myocardium is also considered. The most common side effects of SGLT2 inhibitors include urinary tract and genital infections, euglycemic ketoacidosis. Other possible side effects include an increased risk of lower limb amputations, Fournier gangrene, breast cancer in women, bladder cancer in men, orthostatic hypotension and acute kidney injury, and an increased tendency to fracture. Most side effects can be avoided through adequate patient education and assessment of risk factors and contraindications before starting the use of drugs. Despite the clear need for more research on SGLT2 inhibitors, their widespread use will positively affect the health of the diabetic patient population.

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Braescu, Laurentiu, Marinica Gaspar, Darius Buriman, Oana Maria Aburel, Adrian-Petru Merce, Felix Bratosin, Klokov Sergei Aleksandrovich, Satish Alambaram et Cristian Mornos. « The Role and Implications of Epicardial Fat in Coronary Atherosclerotic Disease ». Journal of Clinical Medicine 11, n^o 16 (12 août 2022) : 4718. http://dx.doi.org/10.3390/jcm11164718.

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The current minireview aims to assess the implications of epicardial fat secretory function in the development of coronary artery disease. The epicardial adipose tissue (EAT) is a visceral fat depot that has been described as a cardiovascular risk factor. In addition to its mechanical protection role and physiological secretory function, it seems that various secretion products of the epicardial fat are responsible for metabolic disturbances at the level of the cardiac muscle when in association with pre-existing pathological conditions, such as metabolic syndrome. There is a pathological reduction in sarcomere shortening, abnormal cytosolic Ca2+ fluxes, reduced expression of sarcoplasmic endoplasmic reticulum ATPase 2a and decreased insulin-mediated Akt-Ser473-phosphorylation in association with abnormal levels of epicardial fat tissue. Activin A, angiopoietin-2, and CD14-positive monocytes selectively accumulate in the diseased myocardium, resulting in reduced cardiomyocyte contractile function. At the same time, it is believed that these alterations in secretory products directly decrease the myocyte function via molecular changes, thus contributing to the development of coronary disease when certain comorbidities are associated.

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Aditya, Suruchi, Suryakant Mathur et Aditya Rattan. « Dapagliflozin : A Novel Therapeutic Approach to Treat Diabetes ». JMS SKIMS 14, n^o 2 (20 décembre 2011) : 43–45. http://dx.doi.org/10.33883/jms.v14i2.81.

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Current approaches to treatment of diabetes have many drawbacks. Most of the oral hypoglycemic drugs target the insulin secretion and action. Sodium Glucose co transporters (SGLT)-2 inhibitors are a recent addition to antihyperglycemic drugs that act by reducing glucose reabsorption from the renal filtrate so that bulk of glucose is excreted in the urine. Dapagliflozin, the first in this new class of drugs, is a SGLT2 inhibitor. It causes loss in body weight and is not associated with major hypoglycemic events.Dapagliflozin is currently in advanced development for use alone or in combination with other hypoglycemic agents. Concerns regarding increased cancer risk have delayed the Food and Drug Authority (FDA) approval of this drug. SGLT2 inhibitors represent a major dvancement in management of type 2 diabetes mellitus (T2DM) as they have shifted the focus onto kidney and act independent of insulin. JMS 2011;14(2):43-45

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Serhiyenko, A. A., et V. A. Serhiyenko. « Diabetic cardiomyopathy : treatment ». INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine) 16, n^o 8 (6 avril 2021) : 669–80. http://dx.doi.org/10.22141/2224-0721.16.8.2020.222888.

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This article presents a review of the scientific literature on some key aspects of the current state of the problem of diabetic cardiomyopathy treatment. Measures aimed at reducing insulin resistance, correction of hyperglycemia, dyslipoproteinemia, myocardial metabolism disorders, prevention and treatment of thrombosis, symptomatic therapy of concomitant diseases and syndromes of arterial hypertension, coronary heart disease, heart failure and arrhythmias should be at the forefront of the treatment for diabetic cardiomyopathy. In this direction it is necessary to carry out the following preventive and therapeutic measures: rational nutrition and physical activity; correction of obesity; limiting salt intake to 2–4 g/day; exclusion of smoking, alcohol consumption, products containing caffeine. In particular, the issues are analyzed related to the peculiarities of rational nutrition and physical activity, optimization of glycemic control (insulin and/or insulin secretagogues, glucagon-like peptide-1 analogues, sodium-glucose cotransporter-2 inhibitors); correction of metabolic disorders in the myocardium (drugs that improve the energy status of cells — potential means of energy supply for the survival of ischemic myocardium), metabolic modulators (metabolic drugs — trimetazidine, perhexiline, ranolazine; L-carnitine); restriction of extracellular Ca2+ entry into cells (calcium channel blockers), the use of β-adrenergic receptor blockers; modulation of oxidative stress (alpha-lipoic acid, benfotiamine); administration of long-chain ω-3 polyunsaturated fatty acids; sulforaphane, coenzyme Q10; magnesium. Also, promising ways in the treatment of diabetic cardiomyopathy (mimetic peptides for restoring L-type Ca2+ channels; noncoding microRNAs and long noncoding RNAs) are considered.

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Srinivas, Karthik, Melvin George et Damal Kandadai Sriram. « Empagliflozin : an exciting prospect in the treatment of diabetes ». International Journal of Basic & ; Clinical Pharmacology 7, n^o 1 (23 décembre 2017) : 1. http://dx.doi.org/10.18203/2319-2003.ijbcp20175669.

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Type 2 diabetes mellitus (T2DM) continues to be a chronic and disabling disease that is associated with high mortality and morbidity. The epidemic burden of diabetes mellitus has increased in developing countries and Asia is considered as the “diabetic epicentre”. Type 2 diabetes (T2DM), is characterised by reduced secretion of insulin from pancreatic beta cells independently or associated with reduced response of peripheral tissues to circulating insulin. A proper glycaemic control is essential to delay the micro and macrovascular complications of T2DM. Standard anti-diabetic agents including insulin happen to induce minor to major adverse outcomes in certain populations over prolonged period of administration. Hence there has been a compelling need to develop newer and novel approach to treatment of T2DM. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are a novel category of drugs that happen to reduce glycaemic overload by inducing glycosuria. The safety, efficacy and tolerability profile of these drugs were studied separately under various trials and was approved for use in August 2014 by US-FDA. This review is an attempt to describe the history of SGLT-2 inhibitors, their mechanism of action, safety and efficacy as well as its current status among anti-diabetic agents.

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Eldesoqui, Mamdouh, Zienab Helmy Eldken, Sally Abdallah Mostafa, Rasha Hamed Al-Serwi, Mohamed El-Sherbiny, Nehal Elsherbiny, Zuhair M. Mohammedsaleh et Noha Hammad Sakr. « Exercise Augments the Effect of SGLT2 Inhibitor Dapagliflozin on Experimentally Induced Diabetic Cardiomyopathy, Possible Underlying Mechanisms ». Metabolites 12, n^o 7 (11 juillet 2022) : 635. http://dx.doi.org/10.3390/metabo12070635.

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One of the most prevalent cardiovascular problems linked with type 2 diabetes mellitus (T2DM) is diabetic cardiomyopathy (DCM). DCM is associated with myocardial oxidative stress, inflammation, apoptosis, suppressed autophagy, extracellular matrix remodeling, and fibrosis. The current study aims to investigate the protective effect of sodium-glucose transport 2 inhibitor (SGLT2i) dapagliflozin and/or exercise on DCM. Thirty adult male Sprague Dawley rats are used. T2DM is induced by a 6-week high-fat diet (HFD) followed by a single intraperitoneal (IP) injection of 35 mg/kg streptozotocin (STZ). Rats are divided into five groups, control, diabetic (DM), DM + swimming, DM + dapagliflozin, and DM + dapagliflozin and swimming. Serum glucose, insulin, insulin resistance (HOMA-IR), and cardiac enzymes (CK-MB and lactate dehydrogenase (LDH) are measured. Heart specimens are used for evaluation of cellular oxidative stress markers malondialdehyde (MDA), antioxidant enzymes, glutathione (GSH), and catalase (CAT), as well as mRNA expression of TGF-β, MMP9, IL-1β, and TNF-α. Stained sections with haematoxylin and eosin (H & E) and Masson trichrome are used for histopathological evaluation and detection of fibrosis, respectively. Immunohistochemical staining for apoptosis (caspase-3), and autophagy (LC3) are also carried out. The combinations of SGLT2i and exercise exhibited the most significant cardioprotective effect. It improved diabetic-induced histopathological alterations in the myocardium and attenuated the elevation of serum blood glucose, CK-MB, LDH, myocardial MDA, and mRNA expression of TNF-α, IL-1β, TGF-β, MMP9, and the immune expression of caspase-3. Moreover, this combination increased the serum insulin, myocardial antioxidants GSH and CAT, and increase the immune expression of the LC-3. In conclusion, a combination of SGLT2i and exercise exerted a better antioxidant, anti-inflammatory, and antifibrotic effect in DCM. Moreover, the combination enhances the autophagic capacity of the heart.

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Soldatov, Vladislav O., Elena A. Shmykova, Marina A. Pershina, Andrey O. Ksenofontov, Yaroslav M. Zamitsky, Alexandr L. Kulikov, Anna A. Peresypkina, Anton P. Dovgan et Yuliya V. Belousova. « Imidazoline receptors agonists : possible mechanisms of endothelioprotection ». Research Results in Pharmacology 4, n^o 2 (19 juillet 2018) : 11–19. http://dx.doi.org/10.3897/rrpharmacology.4.27221.

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Imidazoline receptor agonists are one of the groups of contemporary antihypertensive drugs with the pleiotropic cardiovascular effects. In this review, the historical, physiological, pathophysiological aspects concerning imidazoline receptor agonists and possible mechanisms for their participation in endothelioprotection were considered. Illuminated the molecular biology of each subtype of imidazoline receptors and their significance in the pharmacological correction of cardiovascular disease. IR type 1 are localized in the brain nucleus, carrying out the descending tonic control of sympathetic activation, as well as in the endothelial cells of the vessels and kidneys. Their activation leads to a decrease in blood pressure, slowing the remodeling of the vascular wall and increasing sodium nares. IR type 2 is expressed predominantly in the adrenal gland, fat and muscle tissues. The physiological effects of their stimulation are associated with an increase in glucose utilization by peripheral tissues. IR type 3 are mainly present in pancreatic cells and are associated with the regulation of insulin secretion. Their stimulation leads to an increase in insulin liberation. Thus, IR agonists are able to improve endothelial function through various mechanisms, including blood pressure reduction, improvement in metabolic profile, and direct positive effects on the vascular wall. Current information on the pharmacological effects of this group compounds allows us to conclude that they are a promising group for correcting endothelial dysfunction and complications associated with it.

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Wang, Guangju, Xiumei Li, Ying Zhou, Jinghai Feng et Minhong Zhang. « Effects of Dietary Chromium Picolinate on Gut Microbiota, Gastrointestinal Peptides, Glucose Homeostasis, and Performance of Heat-Stressed Broilers ». Animals 12, n^o 7 (27 mars 2022) : 844. http://dx.doi.org/10.3390/ani12070844.

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The current research was devoted to evaluating the effects on gut microbiota, gastrointestinal peptides, and glucose homeostasis of chromium picolinate applied to heat-stressed broilers. In a 14 d experiment, 220 28-day-old AA broilers were randomly assigned into one thermal-neutral and three high-temperature groups dietary-supplemented with 0, 0.4, or 0.8 mg/kg of chromium as chromium picolinate. The temperature for the thermal-neutral group was set at 21 °C, while that for the other three groups (high temperature) was set at 31 °C. The results showed that the average daily gain and average daily feed intake of the 0.4 mg/kg chromium-supplemented group significantly increased compared with the high-temperature groups (p < 0.05). The content of cholecystokinin in the 0.4 mg/kg group significantly decreased, and the gastric inhibitory polypeptide level was significantly elevated in jejunum (p < 0.05). The cecal microbiota of heat-stressed broilers was substantially different from that of the thermal-neutral group. After diet-supplemented chromium, compared to the high-temperature groups, the 0.4 mg/kg chromium supplemented group was characterized by a reduction of Actinobacteriota and Proteobacteria at the phylum level. The Bacilli were elevated, while proportions of Coriobacteria and Gammaproteobacteria were reduced significantly at the class level. The proportions of Lactobacillaceae, Christensenellaceae, and Erysipelotrichaceae were elevated significantly, while that of Clostridiaceae was reduced significantly at the family level. The proportion of Turicibacter was elevated significantly and the proportions of Olsenella and Ruminococcus were reduced significantly at the genus level (p < 0.05). Compared to the high-temperature groups, in the 0.4 mg/kg chromium-supplemented group, the insulin concentration and insulin resistance index were reduced (p < 0.05), and sodium-glucose transporter 1 expression was up-regulated in jejunum (p < 0.05). Performance, microbiota, gastrointestinal peptides, or serum parameters of the 0.8 mg/kg group were almost unaffected by chromium compared with the high-temperature groups. In conclusion, diet supplemented with 0.4 mg/kg Cr improved performance, insulin resistance and sodium-glucose transporter 1 expression and altered gut microflora structure and secretion of gastrointestinal peptides, thus showing that supplementation with chromium is beneficial to maintain glucose homeostasis and alleviate heat stress.

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Bergman, E. N. « Energy contributions of volatile fatty acids from the gastrointestinal tract in various species ». Physiological Reviews 70, n^o 2 (1 avril 1990) : 567–90. http://dx.doi.org/10.1152/physrev.1990.70.2.567.

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The VFA, also known as short-chain fatty acids, are produced in the gastrointestinal tract by microbial fermentation of carbohydrates and endogenous substrates, such as mucus. This can be of great advantage to the animal, since no digestive enzymes exist for breaking down cellulose or other complex carbohydrates. The VFA are produced in the largest amounts in herbivorous animal species and especially in the forestomach of ruminants. The VFA, however, also are produced in the lower digestive tract of humans and all animal species, and intestinal fermentation resembles that occurring in the rumen. The principal VFA in either the rumen or large intestine are acetate, propionate, and butyrate and are produced in a ratio varying from approximately 75:15:10 to 40:40:20. Absorption of VFA at their site of production is rapid, and large quantities are metabolized by the ruminal or large intestinal epithelium before reaching the portal blood. Most of the butyrate is converted to ketone bodies or CO2 by the epithelial cells, and nearly all of the remainder is removed by the liver. Propionate is similarly removed by the liver but is largely converted to glucose. Although species differences exist, acetate is used principally by peripheral tissues, especially fat and muscle. Considerable energy is obtained from VFA in herbivorous species, and far more research has been conducted on ruminants than on other species. Significant VFA, however, are now known to be produced in omnivorous species, such as pigs and humans. Current estimates are that VFA contribute approximately 70% to the caloric requirements of ruminants, such as sheep and cattle, approximately 10% for humans, and approximately 20-30% for several other omnivorous or herbivorous animals. The amount of fiber in the diet undoubtedly affects the amount of VFA produced, and thus the contribution of VFA to the energy needs of the body could become considerably greater as the dietary fiber increases. Pigs and some species of monkey most closely resemble humans, and current research should be directed toward examining the fermentation processes and VFA metabolism in those species. In addition to the energetic or nutritional contributions of VFA to the body, the VFA may indirectly influence cholesterol synthesis and even help regulate insulin or glucagon secretion. In addition, VFA production and absorption have a very significant effect on epithelial cell growth, blood flow, and the normal secretory and absorptive functions of the large intestine, cecum, and rumen. The absorption of VFA and sodium, for example, seem to be interdependent, and release of bicarbonate usually occurs during VFA absorption.(ABSTRACT TRUNCATED AT 400 WORDS)

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Andre, E., E. Yaniz-Galende, C. Hamilton, G. J. Dusting, N. Hellen, CE Poulet, M. Diez Cunado et al. « Poster session 1Cell growth, differentiation and stem cells - Heart72Understanding the metabolism of cardiac progenitor cells : a first step towards controlling their proliferation and differentiation?73Expression of pw1/peg3 identifies a new cardiac adult stem cell population involved in post-myocardial infarction remodeling74Long-term stimulation of iPS-derived cardiomyocytes using optogenetic techniques to promote phenotypic changes in E-C coupling75Benefits of electrical stimulation on differentiation and maturation of cardiomyocytes from human induced pluripotent stem cells76Constitutive beta-adrenoceptor-mediated cAMP production controls spontaneous automaticity of human induced pluripotent stem cell-derived cardiomyocytes77Formation and stability of T-tubules in cardiomyocytes78Identification of miRNAs promoting human cardiomyocyte proliferation by regulating Hippo pathway79A direct comparison of foetal to adult epicardial cell activation reveals distinct differences relevant for the post-injury response80Role of neuropilins in zebrafish heart regeneration81Highly efficient immunomagnetic purification of cardiomyocytes derived from human pluripotent stem cells82Cardiac progenitor cells posses a molecular circadian clock and display large 24-hour oscillations in proliferation and stress tolerance83Influence of sirolimus and everolimus on bone marrow-derived mesenchymal stem cell biology84Endoglin is important for epicardial behaviour following cardiac injuryCell death and apoptosis - Heart87Ultrastructural alterations reflecting Ca2+ handling and cell-to-cell coupling disorders precede occurrence of severe arrhythmias in intact animal heart88Urocortin-1 promotes cardioprotection through ERK1/2 and EPAC pathways : role in apoptosis and necrosis89Expression p38 MAPK and Cas-3 in myocardium LV of rats with experimental heart failure at melatonin and enalapril introductionTranscriptional control and RNA species - Heart92Accumulation of beta-amyloid 1-40 in HF patients : the role of lncRNA BACE1-AS93Role of miR-182 in zebrafish and mouse models of Holt-Oram syndrome94Mir-27 distinctly regulates muscle-enriched transcription factors and growth factors in cardiac and skeletal muscle cells95AF risk factors impair PITX2 expression leading to Wnt-microRNA-ion channel remodelingCytokines and cellular inflammation - Heart98Post-infarct survival depends on the interplay of monocytes, neutrophils and interferon gamma in a mouse model of myocardial Infarction99Inflammatory cd11b/c cells play a protective role in compensated cardiac hypertrophy by promoting an orai3-related pro-survival signal100Anti-inflammatory effects of endothelin receptor blockade in the atrial tissue of spontaneously hypertensive rats101Mesenchymal stromal cells reduce NLRP3 inflammasome activity in Coxsackievirus B3-induced myocarditis102Mesenchymal stromal cells modulate monocytes trafficking in Coxsackievirus B3-induced myocarditis103The impact of regulatory T lymphocytes on long-term mortality in patients with chronic heart failure104Temporal dynamics of dendritic cells after ST-elevation myocardial infarction relate with improvement of myocardial functionGrowth factors and neurohormones - Heart107Preconditioning of hypertrophied heart : miR-1 and IGF-1 crosstalk108Modulation of catecholamine secretion from human adrenal chromaffin cells by manipulation of G protein-coupled receptor kinase-2 activity109Evaluation of cyclic adenosin-3,5- monophosphate and neurohormones in patients with chronic heart failureNitric oxide and reactive oxygen species - Heart112Hydrogen sulfide donor inhibits oxidative and nitrosative stress, cardiohemodynamics disturbances and restores cNOS coupling in old rats113Role and mechanisms of action of aldehydes produced by monoamine oxidase A in cardiomyocyte death and heart failure114Exercise training has contrasting effects in myocardial infarction and pressure-overload due to different endothelial nitric oxide synthase regulation115S-Nitroso Human Serum Albumin dose-dependently leads to vasodilation and alters reactive hyperaemia in coronary arteries of an isolated mouse heart model116Modulating endothelial nitric oxide synthase with folic acid attenuates doxorubicin-induced cardiomyopathy119Effects of long-term very high intensity exercise on aortic structure and function in an animal model120Electron paramagnetic resonance spectroscopy quantification of nitrosylated hemoglobin (HbNO) as an index of vascular nitric oxide bioavailability in vivo121Deletion of repressor activator protein 1 impairs acetylcholine-induced relaxation due to production of reactive oxygen speciesExtracellular matrix and fibrosis - Heart124MicroRNA-19b is associated with myocardial collagen cross-linking in patients with severe aortic stenosis. Potential usefulness as a circulating biomarker125A new ex vivo model to study cardiac fibrosis126Heterogeneity of fibrosis and fibroblast differentiation in the left ventricle after myocardial infarction127Effect of carbohydrate metabolism degree compensation to the level of galectin-3 changes in hypertensive patients with chronic heart failure and type 2 diabetes mellitus128Statin paradox in association with calcification of bicuspid aortic valve interstitial cells129Cardiac function remains impaired despite reversible cardiac fibrosis after healed experimental viral myocarditisIon channels, ion exchangers and cellular electrophysiology - Heart132Identifying a novel role for PMCA1 (Atp2b1) in heart rhythm instability133Mutations of the caveolin-3 gene as a predisposing factor for cardiac arrhythmias134The human sinoatrial node action potential : time for a computational model135iPSC-derived cardiomyocytes as a model to dissect ion current alterations of genetic atrial fibrillation136Postextrasystolic potentiation in healthy and diseased hearts : effects of the site of origin and coupling interval of the preceding extrasystole137Absence of Nav1.8-based (late) sodium current in rabbit cardiomyocytes and human iPSC-CMs138hiPSC-derived cardiomyocytes from Brugada Syndrome patients without identified mutations do not exhibit cellular electrophysiological abnormalitiesMicrocirculation141Atherogenic indices, collagen type IV turnover and the development of microvascular complications- study in diabetics with arterial hypertension142Changes in the microvasculature and blood viscosity in women with rheumatoid arthritis, hypercholesterolemia and hypertensionAtherosclerosis145Shear stress regulates endothelial autophagy : consequences on endothelial senescence and atherogenesis146Obstructive sleep apnea causes aortic remodeling in a chronic murine model147Aortic perivascular adipose tissue displays an aged phenotype in early and late atherosclerosis in ApoE-/- mice148A systematic evaluation of the cellular innate immune response during the process of human atherosclerosis149Inhibition of Coagulation factor Xa increases plaque stability and attenuates the onset and progression of atherosclerotic plaque in apolipoprotein e-deficient mice150Regulatory CD4+ T cells from patients with atherosclerosis display pro-inflammatory skewing and enhanced suppression function151Hypoxia-inducible factor (HIF)-1alpha regulates macrophage energy metabolism by mediating miRNAs152Extracellular S100A4 is a key player of smooth muscle cell phenotypic transition : implications in atherosclerosis153Microparticles of healthy origins improve atherosclerosis-associated endothelial progenitor cell dysfunction via microRNA transfer154Arterial remodeling and metabolism impairment in early atherosclerosis155Role of pannexin1 in atherosclerotic plaque formationCalcium fluxes and excitation-contraction coupling158Amphiphysin II induces tubule formation in cardiac cells159Interleukin 1 beta regulation of connexin 43 in cardiac fibroblasts and the effects of adult cardiac myocyte:fibroblast co-culture on myocyte contraction160T-tubular electrical defects contribute to blunted beta-adrenergic response in heart failure161Beat-to-beat variability of intracellular Ca2+ dynamics of Purkinje cells in the infarct border zone of the mouse heart revealed by rapid-scanning confocal microscopy162The efficacy of late sodium current blockers in hypertrophic cardiomyopathy is dependent on genotype : a study on transgenic mouse models with different mutations163Synthesis of cADPR and NAADP by intracellular CD38 in heart : role in inotropic and arrhythmogenic effects of beta-adrenoceptor signalingContractile apparatus166Towards an engineered heart tissue model of HCM using hiPSC expressing the ACTC E99K mutation167Diastolic mechanical load delays structural and functional deterioration of ultrathin adult heart slices in culture168Structural investigation of the cardiac troponin complex by molecular dynamics169Exercise training restores myocardial and oxidative skeletal muscle function from myocardial infarction heart failure ratsOxygen sensing, ischaemia and reperfusion172A novel antibody specific to full-length stromal derived factor-1 alpha reveals that remote conditioning induces its cleavage by endothelial dipeptidyl peptidase 4173Attenuation of myocardial and vascular arginase activity by vagal nerve stimulation via a mechanism involving alpha-7 nicotinic receptor during cardiac ischemia and reperfusion174Novel nanoparticle-mediated medicine for myocardial ischemia-reperfusion injury simultaneously targeting mitochondrial injury and myocardial inflammation175Acetylcholine plays a key role in myocardial ischaemic preconditioning via recruitment of intrinsic cardiac ganglia176The role of nitric oxide and VEGFR-2 signaling in post ischemic revascularization and muscle recovery in aged hypercholesterolemic mice177Efficacy of ischemic preconditioning to protect the human myocardium : the role of clinical conditions and treatmentsCardiomyopathies and fibrosis180Plakophilin-2 haploinsufficiency leads to impaired canonical Wnt signaling in ARVC patient181Improved technique for customized, easier, safer and more reliable transverse aortic arch banding and debanding in mice as a model of pressure overload hypertrophy182Late sodium current inhibitors for the treatment of inducible obstruction and diastolic dysfunction in hypertrophic cardiomyopathy : a study on human myocardium183Angiotensin II receptor antagonist fimasartan has protective role of left ventricular fibrosis and remodeling in the rat ischemic heart184Role of High-Mobility Group Box 1 (HMGB1) redox state on cardiac fibroblasts activities and heart function after myocardial infarction185Atrial remodeling in hypertrophic cardiomyopathy : insights from mouse models carrying different mutations in cTnT186Electrophysiological abnormalities in ventricular cardiomyocytes from a Maine Coon cat with hypertrophic cardiomyopathy : effects of ranolazine187ZBTB17 is a novel cardiomyopathy candidate gene and regulates autophagy in the heart188Inhibition of SRSF4 in cardiomyocytes induces left ventricular hypertrophy189Molecular characterization of a novel cardiomyopathy related desmin frame shift mutation190Autonomic characterisation of electro-mechanical remodeling in an in-vitro leporine model of heart failure191Modulation of Ca2+-regulatory function by three novel mutations in TNNI3 associated with severe infant restrictive cardiomyopathyAging194The aging impact on cardiac mesenchymal like stromal cells (S+P+)195Reversal of premature aging markers after bariatric surgery196Sex-associated differences in vascular remodeling during aging : role of renin-angiotensin system197Role of the receptor for advanced glycation end-products (RAGE) in age dependent left ventricle dysfunctionsGenetics and epigenetics200hsa-miR-21-5p as a key factor in aortic remodeling during aneurysm formation201Co-inheritance of mutations associated with arrhythmogenic and hypertrophic cardiomyopathy in two Italian families202Lamin a/c hot spot codon 190 : form various amino acid substitutions to clinical effects203Treatment with aspirin and atorvastatin attenuate cardiac injury induced by rat chest irradiation : Implication of myocardial miR-1, miR-21, connexin-43 and PKCGenomics, proteomics, metabolomics, lipidomics and glycomics206Differential phosphorylation of desmin at serines 27 and 31 drives the accumulation of preamyloid oligomers in heart failure207Potential role of kinase Akt2 in the reduced recovery of type 2 diabetic hearts subjected to ischemia / reperfusion injury208A proteomics comparison of extracellular matrix remodelling in porcine coronary arteries upon stent implantationMetabolism, diabetes mellitus and obesity211Targeting grk2 as therapeutic strategy for cancer associated to diabetes212Effects of salbutamol on large arterial stiffness in patients with metabolic syndrome213Circulating microRNA-1 and microRNA-133a : potential biomarkers of myocardial steatosis in type 2 diabetes mellitus214Anti-inflammatory nutrigenomic effects of hydroxytyrosol in human adipocytes - protective mechanisms of mediterranean diets in obesity-related inflammation215Alterations in the metal content of different cardiac regions within a rat model of diabetic cardiomyopathyTissue engineering218A novel conductive patch for application in cardiac tissue engineering219Establishment of a simplified and improved workflow from neonatal heart dissociation to cardiomyocyte purification and characterization220Effects of flexible substrate on cardiomyocytes cell culture221Mechanical stretching on cardiac adipose progenitors upregulates sarcomere-related genes ». Cardiovascular Research 111, suppl 1 (1 juillet 2016) : S16—S42. http://dx.doi.org/10.1093/cvr/cvw135.

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Xu, Bo, Shaoqian Li, Bo Kang et Jiecan Zhou. « The current role of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes mellitus management ». Cardiovascular Diabetology 21, n^o 1 (25 mai 2022). http://dx.doi.org/10.1186/s12933-022-01512-w.

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AbstractType 2 diabetes mellitus (T2DM) is a chronic, complex metabolic disease characterized by chronic hyperglycemia causing from insufficient insulin signaling because of insulin resistance or defective insulin secretion, and may induce severe complications and premature death. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are oral drugs used to reduce hyperglycemia in patients with T2DM, including empagliflozin, ertugliflozin, dapagliflozin and canagliflozin. The primary objective of this article is to examine the clinical benefit, safety, and tolerability of the four SGLT2 inhibitors approved by the US FDA. SGLT2 inhibitors increase urinary glucose excretion via inhibiting SGLT2 to decrease renal reabsorption of filtered glucose and reduce the renal threshold for glucose. Rather than stimulating insulin release, SGLT2 inhibitors improve β-cell function by improving glucotoxicity, as well as reduce insulin resistance and increase insulin sensitivity. Early clinical trials have confirmed the beneficial effects of SGLT2 in T2DM with acceptable safety and excellent tolerability. In recent years, SGLT2 inhibitors has been successively approved by the FDA to decrease cardiovascular death and decrease the risk of stroke and cardiac attack in T2DM adults who have been diagnosed with cardiovascular disease, treating heart failure (HF) with reduced ejection fraction and HF with preserved ejection fraction, and treat diabetic kidney disease (DKD), decrease the risk of hospitalization for HF in T2DM and DKD patients. SGLT2 inhibitors are expected to be an effective treatment for T2DM patients with non alcoholic fatty liver disease. SGLT2 inhibitors have a similar safety profile to placebo or other active control groups, with major adverse events such as Ketoacidosis or hypotension and genital or urinary tract infections.

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Hropot, Tim, Tadej Battelino et Klemen Dovc. « Sodium-glucose co-transporter-2 inhibitors in Type 1 Diabetes : A Scoping Review ». Hormone Research in Paediatrics, 24 octobre 2022. http://dx.doi.org/10.1159/000527653.

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Background. With recent developments in diabetes technology, attaining adequate glucose control is more achievable than ever. Despite these improvements a significant proportion of individuals with type 1 diabetes (T1D) do not reach recommended glycaemic goals. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are glucose-lowering agents that inhibit the reabsorption of filtered glucose in the kidneys, thus promoting glucosuria. Because the glucose-lowering effect of SGLT2 inhibitors is achieved independently of insulin secretion, it has been speculated whether they could bridge the gap towards achieving glycaemic targets in individuals with T1D. Objectives. Our main goal was to systematically map the current knowledge on the efficacy and safety of SGLT2 inhibitor use in adults with T1D and present recent studies regarding the use of SGLT2 inhibitors in youth with T1D. Design. Using a scoping review approach, we searched MEDLINE to identify relevant clinical trials of SGLT2 inhibitors as adjunctive therapy to insulin in T1D published from 31-January-2012, to 31-January-2022. We included the most relevant, large-scale (> 300 participants), and long (>18 weeks) placebo controlled clinical trials of SGLT2 inhibitors as an add-on therapy to insulin in adults T1D. Additionally, we included all relevant pilot studies evaluating the use of SGLT2 inhibitors as add-on therapy to insulin in youths with T1D. Finally, we summarized data on glycaemic outcomes and potential safety concerns. Results. We identified eight placebo controlled clinical trials in adults with T1D meeting our inclusion criteria. Additionally, we identified two relevant pilot studies in youth with T1D. The clinical trials in adults with T1D confirmed the efficacy of SGLT2 inhibitors as add-on therapy to insulin. However, this was associated with an increased incidence of DKA versus placebo in all identified clinical trials. The two relevant pilot studies in youths with T1D showed promising results of SGLT2 inhibitor use as an add-on therapy to insulin, especially when combined with a fully closed-loop system. Conclusions. SGLT2 inhibitors, as an add-on therapy to insulin, improve glycaemic outcomes in adults with T1D with a potential cost of increasing the risk of DKA. The use of add-on SGLT2 inhibitors to insulin show promising results in youths with T1D. Moreover, SGLT2 inhibitors as add-on therapy in combination with closed-loop insulin therapy could provide additional benefits in improving glycemic control. The current role of SGLT2 inhibitors as an adjunct therapy to insulin in individuals with type 1 diabetes is yet to be determined.

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Kovalchuk A. V., Zinich O. V., Prybyla O. V., Kushnareva N. M., Kovalchuk V. M. et Shyshkan-Shyshova K. O. « OSTEOCALCIN ROLE IN THE REGULATION OF INSULIN SECRETION AND OSTEOTROPIC EFFECTS OF DIFFERENT CLASSES OF ANTI-DIABETIC DRUGS (LITERATURE REVIEW AND OWN RESEARCH) ». World Science, n^o 3(75) (8 mai 2022). http://dx.doi.org/10.31435/rsglobal_ws/30042022/7803.

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Background. Current data suggest that bone tissue produces hormonally active factors - modulators of metabolic processes throughout the body. The most significant osteoproteins is osteocalcin, the non-collagen structural protein of the bone matrix, which is synthesized by osteoblasts and enters the bloodstream during the resorption of bone tissue. Osteocalcin is involved in the regulation of energy balance, insulin secretion, peripheric insulin sensitivity, and adipocyte’s function, while being an important marker of bone remodeling. The aim of this study was to investigate the relationship between osteocalcin levels and metabolic parameters in 97 patients with type 2 diabetes over 50 years of age, in the course of pharmacotherapy using different classes of antidiabetic drugs, namely human insulin, glucagon-like peptide-1 agonists (aGLP), and sodium-glucose co-transporter 2 (SGLT2) inhibitors, depending on presence of obesity. Results. There was found the highest serum osteocalcin level in patients without obese who received a metabolically active therapy with insulin or aGLP-1, comparing to nonobese subjects of SGLT2 inhibitors therapy group. The lowest level of HbA1c and triglycerides observed in non-obese patients on the background of taking aGLP-1. Conclusion. It can be assumed that the factor determining the hypoglycemic efficacy of investigated drugs may be the pathogenesis of type 2 diabetes which depends on the degree of obesity, while the type of antidiabetic therapy has a corrective effect, probably mediated by changes in body weight and fat distribution.

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Kale, Ajinath, Anshima Sharma, Hans-Joachim Anders et Anil Bhanudas Gaikwad. « Diabetes and Cardiorenal Complications : A Clinical Review of Existing Therapies and Novel Combinations, Focusing on SGLT2 Inhibitors ». Current Diabetes Reviews 19 (16 août 2022). http://dx.doi.org/10.2174/1573399819666220816145907.

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Abstract: Type 2 diabetes mellitus (T2DM) is a set of metabolic disorders specified by hyperglycemia as a result of abnormalities in insulin secretion or sensitivity. Chronic kidney disease (CKD) and cardiovascular disease (CVD) are the widespread co-morbidities of T2DM and share risk factors for onset and progression. Despite numerous mono- and combination therapies exist, the progression of diabetes complications remains a global health concern. Treatment options for diabetic- CKD and CVD include drugs targeting hyperglycemia, hypertension, albuminuria, hyperlipidemia and the renin-angiotensin aldosterone system (RAAS). The sodium-glucose co-transporter 2 channel (SGLT2) is abundantly present in proximal tubules of the kidney and its capacity to recover glucose and sodium from the glomerular filtrate limits urinary glucose and sodium excretion. SGLT2 inhibitors (SGLT2i) reduce sodium and glucose reabsorption in the proximal and thus increase urinary glucose excretion in T2DM. SGLT2i monotherapy can improve but dual SGLT2/RAAS inhibition or SGLT2i along with other classes of drugs are more effective in protecting the kidneys and the cardiovascular system in patients with and without diabetes. Combinations such as empagliflozin and linagliptin, ertugliflozin and metolazone, dapagliflozin and sacubitril-valsartan and many more show promising results. Here, we have reviewed the ongoing and completed clinical trials, addressed current theories, and discussed necessary future research to explain the possible risks and benefits of using an SGLT2i alone and in combination with existing antidiabetic drugs and drugs acting on the cardiovascular system.

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Gronda, Edoardo, Mariell Jessup, Massimo Iacoviello, Alberto Palazzuoli et Claudio Napoli. « Glucose Metabolism in the Kidney : Neurohormonal Activation and Heart Failure Development ». Journal of the American Heart Association 9, n^o 23 (décembre 2020). http://dx.doi.org/10.1161/jaha.120.018889.

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Abstract The liver is not the exclusive site of glucose production in humans in the postabsorptive state. Robust data support that the kidney is capable of gluconeogenesis and studies have demonstrated that renal glucose production can increase systemic glucose production. The kidney has a role in maintaining glucose body balance, not only as an organ for gluconeogenesis but by using glucose as a metabolic substrate. The kidneys reabsorb filtered glucose through the sodium‐glucose cotransporters sodium‐glucose cotransporter (SGLT) 1 and SGLT2, which are localized on the brush border membrane of the early proximal tubule with immune detection of their expression in the tubularized Bowman capsule. In patients with diabetes mellitus, the renal maximum glucose reabsorptive capacity, and the threshold for glucose passage into the urine, are higher and contribute to the hyperglycemic state. The administration of SGLT2 inhibitors to patients with diabetes mellitus enhances sodium and glucose excretion, leading to a reduction of the glycosuria threshold and tubular maximal transport of glucose. The net effects of SGLT2 inhibition are to drive a reduction in plasma glucose levels, improving insulin secretion and sensitivity. The benefit of SGLT2 inhibitors goes beyond glycemic control, since inhibition of renal glucose reabsorption affects blood pressure and improves the hemodynamic profile and the tubule glomerular feedback. This action acts to rebalance the dense macula response by restoring adenosine production and restraining renin‐angiotensin‐aldosterone activation. By improving renal and cardiovascular function, we explain the impressive reduction in adverse outcomes associated with heart failure supporting the current clinical perspective.

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Wang, Haitao, Yuqian Liu et Duofu Peng. « PO-020 Aerobic Exercise Attenuates Myocardial Injury Through Activation of SIRT1 Signaling in T2DM Rats ». Exercise Biochemistry Review 1, n^o 3 (3 octobre 2018). http://dx.doi.org/10.14428/ebr.v1i3.9333.

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Objective Myocardial injury caused by elevated blood glucose is a major risk factor for type 2 diabetes mellitus (T2DM) cardiomyopathy. Aerobic exercise can significantly improve the energy metabolism and is widely used in clinic to prevent and cure T2DM and other metabolic diseases. Myocardial injury can be attenuated after aerobic exercise. Some researches showed SIRT1 is a histone deacetylation enzyme activated by NAD+/NADH, and mainly distributes in the heart, liver, etc. SIRT1 plays an important role in controlling the insulin secretion, which can regulate glucose and lipid metabolism and some other important biological functions. It is not known whether the myocardial injury was reduced by regulating the level of SIRT1 after aerobic exercise. The purpose of the research was to illustrate the regulatory mechanism of decreased myocardial injury after aerobic exercise, and provided theoretical basis for early prevention and treatment of T2DM myocardial injury. Methods There were two stages in the experiment. At the first stage, 30 male SD rats,12-month old, were randomly divided into two groups, the control group (CC, fed with standard diet and kept sedentary, 8 rats), the high-sugar-lipid fodder for T2DM model Group (DC, kept sedentary, 22 rats). High sugar and high fat diet formula for 10% lard, 20% sucrose, egg yolk powder 8%, 0.1% sodium deoxycholate, 61.9% basic feed, AIN-93g, provided by animal experimental center of Hebei Province. After 5-week high-sugar-lipid fodder, the DC rats were injected streptozocin (STZ, 35mg/kg), the FBG of the tail vein were measured after 12h, and FBG≥7.0mmol/L was defined as T2DM model. Six rats were excluded because of low FBG (<7.0mmol/L). At the second stage, all of the rats were fed with standard diet. The T2DM rats were randomly assigned to the T2DM group (DC, kept sedentary, 8 rats) and T2DM combined with aerobic exercise, (DE, run on treadmill at 15m/min～19m/min, 45min/d, slope 5%, 6d/w, 5W, 8 rats). The myocardial tissue sections were stained with hematoxylin and eosin (HE) to observe the histological changes. The level of serum insulin was examined by ELISA kits. The content of serum glucose, the activity of SOD and the content of MDA in heart were examined by reagent kits after 5 weeks. The expression of SIRT1 protein in heart were measured using Western blot. ELISA kits were used for the determination of the NAD+/NADH ratio. Results (1) The myocardial sections of CC can be observed clear cell contour, bright color, arranged closely and neatly, and nuclear distribution in cells border and nuclei of uniform size. In DC myocardial sections, myocardial cell contour was fuzzy, nuclei were relatively large, reduced the number of nuclei and inward migration. The broken cells and part of the cells and nuclei overflow can also be seen. The shape of nucleus was irregular and shifted to the internal. In myocardial cell sections of DE rats, the cell profile was relatively clear, and arranged more orderly, a larger number of nuclei, generated less shift. (2) The plasma insulin of DE were obviously lower than that of DC (P<0.01). The content of serum glucose of DE was significantly decreased compared with that of DC (P<0.01). (3) The ratio of NAD+/NADH in DE heart was higher than that of DC (P<0.05). (4) The expression of SIRT1 in DE heart was higher than that of DC (P<0.05). (5)The activity of SOD in DE heart was increased while the content of MDA in DE was significantly decreased compared with those in DC (P<0.01). Conclusions Aerobic exercise can effectively reduced the blood glucose level of T2DM rats. The NAD+/NADH ratio in the myocardium of T2DM rats were increased after the aerobic exercise. As a result, the content of SIRT1 protein in myocardial cells of T2DM rats were increased after the aerobic exercise, which resulted in the increased SOD activity and antioxidant capacity in the cardiac muscle cells, which lead to the attenuated myocardial injury in T2DM rats .

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