Teneligliptin mitigates diabetic cardiomyopathy by inhibiting activation of the NLRP3 inflammasome

BACKGROUND Diabetic cardiomyopathy(DCM),which is a complication of diabetes,poses a great threat to public health.Recent studies have confirmed the role of NLRP3(NOD-like receptor protein 3)activation in DCM development through the inflammatory response.Teneligliptin is an oral hypoglycemic dipeptidyl peptidase-IV inhibitor used to treat diabetes.Teneligliptin has recently been reported to have anti-inflammatory and protective effects on myocardial cells.AIM To examine the therapeutic effects of teneligliptin on DCM in diabetic mice.METHODS Streptozotocin was administered to induce diabetes in mice,followed by treatment with 30 mg/kg teneligliptin.RESULTS Marked increases in cardiomyocyte area and cardiac hypertrophy indicator heart weight/tibia length reductions in fractional shortening,ejection fraction,and heart rate;increases in creatine kinase-MB(CK-MB),aspartate transaminase(AST),and lactate dehydrogenase(LDH)levels;and upregulated NADPH oxidase 4 were observed in diabetic mice,all of which were significantly reversed by teneligliptin.Moreover,NLRP3 inflammasome activation and increased release of interleukin-1βin diabetic mice were inhibited by teneligliptin.Primary mouse cardiomyocytes were treated with high glucose(30 mmol/L)with or without teneligliptin(2.5 or 5μM)for 24 h.NLRP3 inflammasome activation.Increases in CKMB,AST,and LDH levels in glucose-stimulated cardiomyocytes were markedly inhibited by teneligliptin,and AMP(p-adenosine 5‘-monophosphate)-p-AMPK(activated protein kinase)levels were increased.Furthermore,the beneficial effects of teneligliptin on hyperglycaemia-induced cardiomyocytes were abolished by the AMPK signaling inhibitor compound C.CONCLUSION Overall,teneligliptin mitigated DCM by mitigating activation of the NLRP3 inflammasome.

Diabetic cardiomyopathy:Emerging therapeutic options

Diabetic cardiomyopathy(DbCM)is a common but underrecognized complication of patients with diabetes mellitus(DM).Although the pathobiology of other cardiac complications of diabetes such as ischemic heart disease and cardiac autonomic neuropathy are mostly known with reasonable therapeutic options,the mechanisms and management options for DbCM are still not fully understood.In its early stages,DbCM presents with diastolic dysfunction followed by heart failure(HF)with preserved ejection fraction that can progress to systolic dysfunction and HF with reduced ejection fraction in its advanced stages unless appropriately managed.Apart from prompt control of DM with lifestyle changes and antidiabetic medications,disease-modifying therapy for DbCM includes prompt control of hypertension and dyslipidemia inherent to patients with DM as in other forms of heart diseases and the use of treatments with proven efficacy in HF.A basic study by Zhang et al,in a recent issue of the World Journal of Diabetes elaborates the potential pathophysiological alterations and the therapeutic role of teneligliptin in diabetic mouse models with DbCM.Although this preliminary basic study might help to improve our understanding of DbCM and offer a potential new management option for patients with the disease,the positive results from such animal models might not always translate to clinical practice as the pathobiology of DbCM in humans could be different.However,such experimental studies can encourage more scientific efforts to find a better solution to treat patients with this enigmatic disease.

Potential mechanism of teneligliptin in the treatment of diabetic cardiomyopathy

Diabetic cardiomyopathy(DCM),a complication of diabetes,poses a significant threat to public health,both its diagnosis and treatment presents challenges.Teneligliptin has promising applications and research implications in the treat-ment of diabetes mellitus.Zhang et al observed the therapeutic effect of tenelig-liptin on cardiac function in mice with DCM.They validated that teneligliptin’s mechanism of action in treating DCM involves cardiomyocyte protection and inhibition of NLRP3 inflammasome activity.Given that the NLRP3 inflammasome plays a crucial role in the onset and progression of DCM,it presents a promising therapeutic target.Nevertheless,further clinical validation is required to ascertain the preventive and therapeutic efficacy of teneligliptin in DCM.

Atorvastatin ameliorated myocardial fibrosis by inhibiting oxidative stress and modulating macrophage polarization in diabetic cardiomyopathy

In this editorial,we commented on the article published in the recent issue of the World Journal of Diabetes.Diabetic cardiomyopathy(DCM)is characterized by myocardial fibrosis,ventricular hypertrophy and diastolic dysfunction in diabetic patients,which can cause heart failure and threaten the life of patients.The pathogenesis of DCM has not been fully clarified,and it may involve oxidative stress,inflammatory stimulation,apoptosis,and autophagy.There is lack of effective therapies for DCM in the clinical practice.Statins have been widely used in the clinical practice for years mainly to reduce cholesterol and stabilize arterial plaques,and exhibit definite cardiovascular protective effects.Studies have shown that statins also have anti-inflammatory and antioxidant effects.We were particularly concerned about the recent findings that atorvastatin alleviated myocardial fibrosis in db/db mice by regulating the antioxidant stress and antiinflammatory effects of macrophage polarization on diabetic myocardium,and thereby improving DCM.

Teneligliptin:A potential therapeutic approach for diabetic cardiomyopathy

In this editorial,we comment on the article by Zhang et al.Diabetes mellitus is a chronic disorder associated with several complications like cardiomyopathy,neuropathy,and retinopathy.Diabetes prevalence is increasing worldwide.Multiple diabetes medications are prescribed based on individual patients’needs.However,the exact mechanisms by which many of these drugs exert their protective effects remain unclear.Zhang et al elucidates molecular mechanisms undelaying cardioprotective effect of the dipeptidyl peptidase-IV inhibitor,teneligliptin.Briefly,teneligliptin alleviates the activation of NOD-like receptor protein 3 inflammasome,a multiprotein complex that plays a pivotal role in regulating the innate immune system and inflammatory signaling.Suppression of NOD-like receptor protein 3 inflammasome activity reduces the expression of cytokines,oxygen radicals and inflammation.These findings highlight teneligliptin as an anti-diabetic cardioprotective reagent.

Macrophage modulation with dipeptidyl peptidase-4 inhibitors:A new frontier for treating diabetic cardiomyopathy?

This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy(DCM)treatment by dipeptidyl peptidase-4(DPP-4)inhibitors.Zhang et al studied teneligliptin,a DPP-4 inhibitor used for diabetes management,and its potential cardioprotective effects in a diabetic mouse model.They suggested teneligliptin administration may reverse established markers of DCM,including cardiac hypertrophy and compromised function.It also inhibited the NLRP3 inflammasome and reduced inflammatory cytokine production in diabetic mice.Macrophages play crucial roles in DCM pathogenesis.Chronic hyperglycemia disturbs the balance between pro-inflammatory(M1)and antiinflammatory(M2)macrophages,favoring a pro-inflammatory state contributing to heart damage.Here,we highlight the potential of DPP-4 inhibitors to modulate macrophage function and promote an anti-inflammatory environment.These compounds may achieve this by elevating glucagon-like peptide-1 levels and potentially inhibiting the NLRP3 inflammasome.Further studies on teneligliptin in combination with other therapies targeting different aspects of DCM could be suggested for developing more effective treatment strategies to improve cardiovascular health in diabetic patients.

Identification of immune feature genes and intercellular profiles in diabetic cardiomyopathy

BACKGROUND Diabetic cardiomyopathy(DCM)is a multifaceted cardiovascular disorder in which immune dysregulation plays a pivotal role.The immunological molecular mechanisms underlying DCM are poorly understood.AIM To examine the immunological molecular mechanisms of DCM and construct diagnostic and prognostic models of DCM based on immune feature genes(IFGs).METHODS Weighted gene co-expression network analysis along with machine learning methods were employed to pinpoint IFGs within bulk RNA sequencing(RNA-seq)datasets.Single-sample gene set enrichment analysis(ssGSEA)facilitated the analysis of immune cell infiltration.Diagnostic and prognostic models for these IFGs were developed and assessed in a validation cohort.Gene expression in the DCM cell model was confirmed through real time-quantitative polymerase chain reaction and western blotting techniques.Additionally,single-cell RNA-seq data provided deeper insights into cellular profiles and interactions.RESULTS The overlap between 69 differentially expressed genes in the DCM-associated module and 2483 immune genes yielded 7 differentially expressed immune-related genes.Four IFGs showed good diagnostic and prognostic values in the validation cohort:Proenkephalin(Penk)and retinol binding protein 7(Rbp7),which were highly expressed,and glucagon receptor and inhibin subunit alpha,which were expressed at low levels in DCM patients(all area under the curves>0.9).SsGSEA revealed that IFG-related immune cell infiltration primarily involved type 2 T helper cells.High expression of Penk(P<0.0001)and Rbp7(P=0.001)was detected in cardiomyocytes and interstitial cells and further confirmed in a DCM cell model in vitro.Intercellular events and communication analysis revealed abnormal cellular phenotype transformation and signaling communication in DCM,especially between mesenchymal cells and macrophages.CONCLUSION The present study identified Penk and Rbp7 as potential DCM biomarkers,and aberrant mesenchymal-immune cell phenotype communication may be an important aspect of DCM pathogenesis.

Diabetic cardiomyopathy:Importance of direct evidence to support the roles of NOD-like receptor protein 3 inflammasome and pyroptosis

Recently,the roles of pyroptosis,a form of cell death induced by activated NODlike receptor protein 3(NLRP3)inflammasome,in the pathogenesis of diabetic cardiomyopathy(DCM)have been extensively investigated.However,most studies have focused mainly on whether diabetes increases the NLRP3 inflammasome and associated pyroptosis in the heart of type 1 or type 2 diabetic rodent models,and whether various medications and natural products prevent the development of DCM,associated with decreased levels of cardiac NLRP3 inflammasome and pyroptosis.The direct link of NLRP3 inflammasome and associated pyroptosis to the pathogenesis of DCM remains unclear based on the limited evidence derived from the available studies,with the approaches of NLRP3 gene silencing or pharmaceutical application of NLRP3 specific inhibitors.We thus emphasize the requirement for more systematic studies that are designed to provide direct evidence to support the link,given that several studies have provided both direct and indirect evidence under specific conditions.This editorial emphasizes that the current investigation should be circumspect in its conclusion,i.e.,not overemphasizing its role in the pathogenesis of DCM with the fact of only significantly increased expression or activation of NLRP3 inflammasome and pyroptosis in the heart of diabetic rodent models.Only clear-cut evidence-based causative roles of NLRP3 inflammasome and pyroptosis in the pathogenesis of DCM can help to develop effective and safe medications for the clinical management of DCM,targeting these biomarkers.

Empagliflozin ameliorates diabetic cardiomyopathy probably via activating AMPK/PGC-1αand inhibiting the RhoA/ROCK pathway

BACKGROUND Diabetic cardiomyopathy(DCM)increases the risk of hospitalization for heart failure(HF)and mortality in patients with diabetes mellitus.However,no specific therapy to delay the progression of DCM has been identified.Mitochondrial dysfunction,oxidative stress,inflammation,and calcium handling imbalance play a crucial role in the pathological processes of DCM,ultimately leading to cardiomyocyte apoptosis and cardiac dysfunctions.Empagliflozin,a novel glucoselowering agent,has been confirmed to reduce the risk of hospitalization for HF in diabetic patients.Nevertheless,the molecular mechanisms by which this agent provides cardioprotection remain unclear.AIM To investigate the effects of empagliflozin on high glucose(HG)-induced oxidative stress and cardiomyocyte apoptosis and the underlying molecular mechanism.METHODS Twelve-week-old db/db mice and primary cardiomyocytes from neonatal rats stimulated with HG(30 mmol/L)were separately employed as in vivo and in vitro models.Echocardiography was used to evaluate cardiac function.Flow cytometry and TdT-mediated dUTP-biotin nick end labeling staining were used to assess apoptosis in myocardial cells.Mitochondrial function was assessed by cellular ATP levels and changes in mitochondrial membrane potential.Furthermore,intracellular reactive oxygen species production and superoxide dismutase activity were analyzed.Real-time quantitative PCR was used to analyze Bax and Bcl-2 mRNA expression.Western blot analysis was used to measure the phosphorylation of AMP-activated protein kinase(AMPK)and myosin phosphatase target subunit 1(MYPT1),as well as the peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α)and active caspase-3 protein levels.RESULTSIn the in vivo experiment, db/db mice developed DCM. However, the treatment of db/db mice with empagliflozin(10 mg/kg/d) for 8 wk substantially enhanced cardiac function and significantly reduced myocardial apoptosis,accompanied by an increase in the phosphorylation of AMPK and PGC-1α protein levels, as well as a decrease inthe phosphorylation of MYPT1 in the heart. In the in vitro experiment, the findings indicate that treatment ofcardiomyocytes with empagliflozin (10 μM) or fasudil (FA) (a ROCK inhibitor, 100 μM) or overexpression of PGC-1α significantly attenuated HG-induced mitochondrial injury, oxidative stress, and cardiomyocyte apoptosis.However, the above effects were partly reversed by the addition of compound C (CC). In cells exposed to HG,empagliflozin treatment increased the protein levels of p-AMPK and PGC-1α protein while decreasing phosphorylatedMYPT1 levels, and these changes were mitigated by the addition of CC. Adding FA and overexpressingPGC-1α in cells exposed to HG substantially increased PGC-1α protein levels. In addition, no sodium-glucosecotransporter (SGLT)2 protein expression was detected in cardiomyocytes.CONCLUSION Empagliflozin partially achieves anti-oxidative stress and anti-apoptotic effects on cardiomyocytes under HGconditions by activating AMPK/PGC-1α and suppressing of the RhoA/ROCK pathway independent of SGLT2.

Integrated mass spectrometry imaging reveals spatial-metabolic alteration in diabetic cardiomyopathy and the intervention effects of ferulic acid

Diabetic cardiomyopathy(DCM)is a metabolic disease and a leading cause of heart failure among people with diabetes.Mass spectrometry imaging(MSI)is a versatile technique capable of combining the molecular specificity of mass spectrometry(MS)with the spatial information of imaging.In this study,we used MSI to visualize metabolites in the rat heart with high spatial resolution and sensitivity.We optimized the air flow-assisted desorption electrospray ionization(AFADESI)-MSI platform to detect a wide range of metabolites,and then used matrix-assisted laser desorption ionization(MALDI)-MSI for increasing metabolic coverage and improving localization resolution.AFADESI-MSI detected 214 and 149 metabolites in positive and negative analyses of rat heart sections,respectively,while MALDI-MSI detected 61 metabolites in negative analysis.Our study revealed the heterogenous metabolic profile of the heart in a DCM model,with over 105 region-specific changes in the levels of a wide range of metabolite classes,including carbohydrates,amino acids,nucleotides,and their derivatives,fatty acids,glycerol phospholipids,carnitines,and metal ions.The repeated oral administration of ferulic acid during 20 weeks significantly improved most of the metabolic disorders in the DCM model.Our findings provide novel insights into the molecular mechanisms underlying DCM and the potential of ferulic acid as a therapeutic agent for treating this condition.

The protective effect and mechanism of rhein on diabetic cardiomyopathy by regulating Sirt1/PGC-1α pathway

Objective:To explore the protective effects of rhein on cardiomyocyte injury in DCM and its possible mecha-nism.Methods:The diabetic model was induced by intraperitoneal injection with streptozotocin and high-fat diet.The mice were randomly divided into control group,DM group,and DM+RH group.After 12 weeks treatment with rhein,the change of fast blood glucose,body weight,and heart weight/body weigh(t HW/BW)were observed.HE and Masson staining were used to evalu-ate myocardial structural damage.Transmission electron microscope was used to observe the myocardial mitochondrial structure.The mRNA levels of Sirt1,PGC-1α,TFAM,ANP,BNP andβ-MHC were quantified by RT-PCR.Sirt1,PGC-1α and TFAM protein levels were estimated by Western blot and IHC.Results:Compared with control group,the blood glucose,HW/BW,ANP,BNP andβ-MHC mRNA of DM group were significantly increased(P<0.05).The structures of myocardium and mitochondria were obviously destroyed in DM group.Sirt1,PGC-1α and TFAM expression were significantly decreased(P<0.05).Compared with DM group,the blood glucose,HW/BW,ANP,BNP and β-MHC mRNA of DM+RH group were decreased(P<0.05).The myocardial and mitochondrial injury were improved.Sirt1,PGC-1α and TFAM expression were significantly increased(P<0.05).Conclusion:Rhein exhibits protective effects on diabetic cardiomyopathy which may be achieved by activating Sirt1/PGC-1α pathway.

Molecular targets and mechanisms of Jiawei Jiaotai Pill on diabetic cardiomyopathy based on network pharmacology

BACKGROUND Jiawei Jiaotai Pill is commonly used in clinical practice to reduce apoptosis,increase insulin secretion,and improve blood glucose tolerance.However,its mechanism of action in the treatment of diabetic cardiomyopathy(DCM)remains unclear,hindering research efforts aimed at developing drugs specifically for the treatment of DCM.AIM To explore the pharmacodynamic basis and molecular mechanism of Jiawei Jiaotai Pill in DCM treatment.METHODS We explored various databases and software,including the Traditional Chinese Medicine Systems Pharmacology Database,Uniport,PubChem,GenCards,String,and Cytoscape,to identify the active components and targets of Jiawei Jiaotai Pill,and the disease targets in DCM.Protein-protein interaction network,gene ontology,and Kyoto Encyclopedia of Genes and Genomes analyses were used to determine the mechanism of action of Jiawei Jiaotai Pill in treating DCM.Molecular docking of key active components and core targets was verified using AutoDock software.RESULTS Total 42 active ingredients and 142 potential targets of Jiawei Jiaotai Pill were identified.There were 100 common targets between the DCM and Jiawei Jiaotai Pills.Through this screening process,TNF,IL6,TP53,EGFR,INS,and other important targets were identified.These targets are mainly involved in the positive regulation of the mitogen-activated protein kinase(MAPK)MAPK cascade,response to xenobiotic stimuli,response to hypoxia,positive regulation of gene expression,positive regulation of cell proliferation,negative regulation of the apoptotic process,and other biological processes.It was mainly enriched in the AGE-RAGE signaling pathway in diabetic complications,DCM,PI3K-Akt,interleukin-17,and MAPK signaling pathways.Molecular docking results showed that Jiawei Jiaotai Pill's active ingredients had good docking activity with DCM's core target.CONCLUSION The active components of Jiawei Jiaotai Pill may play a role in the treatment of DCM by reducing oxidative stress,cardiomyocyte apoptosis and fibrosis,and maintaining metabolic homeostasis.

Jianpi Qinghua Formula Alleviates Diabetic Myocardial Injury Through Inhibiting JunB/c-Fos Expression

Objective Diabetic cardiomyopathy(DCM)represents a substantial risk factor for heart failure and increased mortality in individuals afflicted with diabetes mellitus(DM).DCM typically manifests as myocardial fibrosis,myocardial hypertrophy,and impaired left ventricular diastolic function.While the clinical utility of the Jianpi Qinghua(JPQH)formula has been established in treating diabetes and insulin resistance,its potential efficacy in alleviating diabetic cardiomyopathy remains uncertain.This study aims to investigate the impact and underlying molecular mechanisms of the JPQH formula(JPQHF)in ameliorating myocardial injury in nonobese diabetic rats,specifically focusing on apoptosis and inflammation.Methods Wistar rats were assigned as the normal control group(CON),while Goto-Kakizaki(GK)rats were randomly divided into three groups:DM,DM treated with the JPQHF,and DM treated with metformin(MET).Following a 4-week treatment regimen,various biochemical markers related to glucose metabolism,cardiac function,cardiac morphology,and myocardial ultrastructure in GK rats were assessed.RNA sequencing was utilized to analyze differential gene expression and identify potential therapeutic targets.In vitro experiments involved high glucose to induce apoptosis and inflammation in H9c2 cells.Cell viability was evaluated using CCK-8 assay,apoptosis was monitored via flow cytometry,and the production of inflammatory cytokines was measured using quantitative real-time PCR(qPCR)and ELISA.Protein expression levels were determined by Western blotting analysis.The investigation also incorporated the use of MAPK inhibitors to further elucidate the mechanism at both the transcriptional and protein levels.Results The JPQHF group exhibited significant reductions in interventricular septal thickness at end-systole(IVSs)and left ventricular internal diameter at end-systole and end-diastole(LVIDs and LVIDd).JPQHF effectively suppressed high glucose-induced activation of IL-1βand caspase 3 in cardiomyocytes.Furthermore,JPQHF downregulated the expression of myocardial JunB/c-Fos,which was upregulated in both diabetic rats and high glucose-treated H9c2 cells.Conclusion The JPQH formula holds promise in mitigating diabetic myocardial apoptosis and inflammation in cardiomyocytes by inhibiting JunB/c-Fos expression through suppressing the MAPK(p38 and ERK1/2)pathway.

Diabetic cardiomyopathy:Pathophysiology,diagnostic evaluation and management

Diabetes affects every organ in the body and cardiovascular disease accounts for two-thirds of the mortality in the diabetic population.Diabetes-related heart disease occurs in the form of coronary artery disease(CAD),cardiac autonomic neuropathy or diabetic cardiomyopathy(DbCM).The prevalence of cardiac failure is high in the diabetic population and DbCM is a common but underestimated cause of heart failure in diabetes.The pathogenesis of diabetic cardiomyopathy is yet to be clearly defined.Hyperglycemia,dyslipidemia and inflammation are thought to play key roles in the generation of reactive oxygen or nitrogen species which are in turn implicated.The myocardial interstitium undergoes alterations resulting in abnormal contractile function noted in DbCM.In the early stages of the disease diastolic dysfunction is the only abnormality,but systolic dysfunction supervenes in the later stages with impaired left ventricular ejection fraction.Transmitral Doppler echocardiography is usually used to assess diastolic dysfunction,but tissue Doppler Imaging and Cardiac Magnetic Resonance Imaging are being increasingly used recently for early detection of DbCM.The management of DbCM involves improvement in lifestyle,control of glucose and lipid abnormalities,and treatment of hypertension and CAD,if present.The role of vasoactive drugs and antioxidants is being explored.This review discusses the pathophysiology,diagnostic evaluation and management options of DbCM.

Mechanisms underlying the impaired contractility of diabetic cardiomyopathy

Cardiac dysfunction is a well-known consequence of diabetes,with sustained hyperglycaemia leading to the development of a cardiomyopathy that is independent of cardiovascular disease or hypertension.Animal models of diabetes are commonly used to study the pathophysiology of diabetic cardiomyopathy,with the hope that increased knowledge will lead ultimately to better therapeutic strategies being developed.At physiological temperature,left ventricular trabeculae isolated from the streptozotocin rat model of type 1 diabetes showed decreased stress and prolonged relaxation,but with no evidence that decreased contractility was a result of altered myocardial Ca2+handling.Although sarcoplasmic reticulum(SR)Ca2+reuptake appeared slower in diabetic trabeculae,it was offset by an increase in actionpotential duration,thereby maintaining SR Ca2+content and favouring increased contraction force.Frequency analysis of t-tubule distribution by confocal imaging of ventricular tissue labeled with wheat germ agglutinin or ryanodine receptor antibodies showed a reduced T-power for diabetic tissue,but the differences were minor in comparison to other models of heart failure.The contractile dysfunction appeared to be the result of disrupted F-actin in conjunction with the increased typeⅠcollagen,with decreased myofilament Ca2+sensitivity contributing to the slowed relaxation.

Trace elements in diabetic cardiomyopathy:An electrophysiological overview

There is a growing body of evidence that Diabetes Mellitus leads to a specific cardiomyopathy apart from vascular disease and bring about high morbidity and mortality throughout the world.Recent clinical and experimental studies have extensively demonstrated that this cardiomyopathy causes impaired cardiac performance manifested by early diastolic and late systolic dysfunction.This impaired cardiac performance most probably have emerged upon the expression and activity of regulatory proteins such as Na+/Ca2+exchanger,sarcoplasmic reticulum Ca2+-ATPase,ryanodine receptor and phospholamban.Over years many therapeutic strategies have been recommended for treatment of diabetic cardiomyopathy.Lately,inorganic elements have been suggested to have anti-diabetic effects due to their suggested ability to regulate glucose homeostasis,reduce oxidative stress or suppress phosphatases.Recent findings have shown that trace elements exert many biological effects including insulin-mimetic or antioxidant activity and in this manner they have been recommended as potential candidates for treatment of diabetes-induced cardiac complications,an effect based on their modes of action.Some of these trace elements are known to play an essential role as component of enzymes and thus modulate the organ function in physiological and pathological conditions.Besides,they can also manipulate redox state of the channels via antioxidant properties and thus contribute to the regulation of [Ca2+]i homeostasis and cardiac ion channels.On account of little information about some trace elements,we discussed the effect of vanadium,selenium,zinc and tungstate on diabetic heart complications.

Role of novel biomarkers in diabetic cardiomyopathy

Diabetic cardiomyopathy(DCM)is commonly defined as cardiomyopathy in patients with diabetes mellitus in the absence of coronary artery disease and hypertension.As DCM is now recognized as a cause of substantial morbidity and mortality among patients with diabetes mellitus and clinical diagnosis is still inappropriate,various expert groups struggled to identify a suitable biomarker that will help in the recognition and management of DCM,with little success so far.Hence,we thought it important to address the role of biomarkers that have shown potential in either human or animal studies and which could eventually result in mitigating the poor outcomes of DCM.Among the array of biomarkers we thoroughly analyzed,long noncoding ribonucleic acids,soluble form of suppression of tumorigenicity 2 and galectin-3 seem to be most beneficial for DCM detection,as their plasma/serum levels accurately correlate with the early stages of DCM.The combination of relatively inexpensive and accurate speckle tracking echocardiography with some of the highlighted biomarkers may be a promising screening method for newly diagnosed diabetes mellitus type 2 patients.The purpose of the screening test would be to direct affected patients to more specific confirmation tests.This perspective is in concordance with current guidelines that accentuate the importance of an interdisciplinary team-based approach.

Is diabetic cardiomyopathy a specific entity?

Diabetes mellitus(DM) is characterised by hyperglycemia, insulin resistance and metabolic dysregulation leading to diastolic and systolic dysfunction in diabetes. In this review, the pathogenetic and pathomorphological changes leading to diastolic and systolic dysfunction in diabetes are discussed. Changes in metabolic signalling pathways, mediators and effectors contribute to the pathogenesis of cardiac dysfunction in DM called diabetic cardiomyopathy(DC). Echocardiographic studies report on the association between DM and the presence of cardiac hypertrophy and myocardial stiffness that lead to diastolic dysfunction. More recently reported echocardiographic studies with more sensitive techniques, such as strain analysis, also observed systolic dysfunction as an early marker of DC. Depression of systolic and diastolic function is continuum and the line of separation is artificial. To conclude, according to current knowledge, DC is expected to be a common single phenotype that is caused by different pathogenetic and pathomorphological changes leading to diastolic and systolic dysfunction in diabetes.

Formononetin alleviates diabetic cardiomyopathy by inhibiting oxidative stress and upregulating SIRT1 in rats

Objective:To evaluate the effect of formononetin on type 2 diabetic cardiomyopathy.Methods:Diabetes was induced by feeding high-fat diet for 2 weeks and administration of 35 mg/kg of streptozotocin in rats.Formononetin was administered at 10,20 and 40 mg/kg for 16 weeks once a day.Plasma glucose,lipid parameters,and cardiac markers in blood samples were measured.Body weight and relative heart weight were recorded.Hemodynamic parameters,oxidative stress parameters and silence information regulator 1(SIRT1)expression in cardiac tissue were estimated.Histopathological changes in cardiac tissue were also observed.Results:Formononetin significantly reduced the levels of glucose,triglycerides,cholesterol,low density lipoprotein,creatine kinaseMB,lactate dehydrogenase and aspartate aminotransferase.In addition,formononetin significantly improved hemodynamic parameters,alleviated oxidative stress and increased SIRT1 expression.Conclusions:The study indicates that formononetin can improve hyperglycemia and hyperlipemia,reduce oxidative stress and increase SIRT1 expression.It can be a potential therapeutic agent for diabetic cardiomyopathy.

Diabetic cardiomyopathy: Pathophysiology, theories and evidence to date

The prevalence of type 2 diabetes(T2D)has increased worldwide and doubled over the last two decades.It features among the top 10 causes of mortality and morbidity in the world.Cardiovascular disease is the leading cause of complications in diabetes and within this,heart failure has been shown to be the leading cause of emergency admissions in the United Kingdom.There are many hypotheses and well-evidenced mechanisms by which diabetic cardiomyopathy as an entity develops.This review aims to give an overview of these mechanisms,with particular emphasis on metabolic inflexibility.T2D is associated with inefficient substrate utilisation,an inability to increase glucose metabolism and dependence on fatty acid oxidation within the diabetic heart resulting in mitochondrial uncoupling,glucotoxicity,lipotoxicity and initially subclinical cardiac dysfunction and finally in overt heart failure.The review also gives a concise update on developments within clinical imaging,specifically cardiac magnetic resonance studies to characterise and phenotype early cardiac dysfunction in T2D.A better understanding of the pathophysiology involved provides a platform for targeted therapy in diabetes to prevent the development of early heart failure with preserved ejection fraction.