The protective effects of liraglutide in reducing lipid droplets accumulation and myocardial fibrosis in diabetic cardiomyopathy

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: Jan. 8, 2025

Diabetes is a primary contributor to diabetic cardiomyopathy (DbCM), which marked by metabolic imbalances such as elevated blood glucose and lipid levels, leading significant structural functional alterations in the myocardium. Elevated free fatty acids (FFAs) hyperglycemia play critical roles DbCM development, with FFAs inducing insulin resistance cardiomyocytes promoting accumulation, resulting oxidative stress fibrosis. Current research suggests that glucagon-like peptide-1 (GLP-1) receptor agonists may effectively mitigate DbCM, although an effective treatment for this condition remains elusive, precise mechanisms of protective effect are not fully understood. In study, we aimed replicate glucolipotoxic conditions treating differentiated H9c2 cells high acids. Additionally, model was induced mice through high-fat diets. Both vitro vivo models were used investigate effects liraglutide on elucidate its underlying molecular mechanisms. Our findings indicate significantly reduces droplet (LD) formation myocardial fibrosis, evidenced decreased expression fibrosis markers, including TGF-β1 collagen types I III. Liraglutide also enhanced AMP-activated protein kinase (AMPK) activation, improved mitochondrial function, increased antioxidant gene expression, signaling, reduced stress. These results demonstrate potential therapeutic role managing diabetes-related cardiac complications, offering comprehensive approach improving outcomes patients diabetes.

Language: Английский

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Critical Appraisal of Pharmaceutical Therapy in Diabetic Cardiomyopathy—Challenges and Prospectives

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 134 - 134

Published: Jan. 20, 2025

Diabetes mellitus (DM) is a multifaceted disorder with pandemic spread and remarkable burden of cardiovascular mortality morbidity. Diabetic cardiomyopathy (DBCM) has been increasingly recognized as the development cardiac dysfunction, which accompanied by heart failure (HF) symptoms in absence obvious reasons like ischemic disease, hypertension, or valvulopathies. Several pathophysiological mechanisms have proposed, including metabolic disorders (e.g., glycation products), oxidative stress, low-grade inflammation, mitochondrial etc., should guide new therapeutic strategies. Up to now, HF treatment not differed between patients without diabetes, limits expected benefits despite high risk former group. However, DBCM may require different management, prioritize anti-diabetic medications testing other novel therapies. This review aims appraise challenges prospectives individualized pharmaceutical therapy for DBCM.

Language: Английский

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Piezo1 deletion mitigates diabetic cardiomyopathy by maintaining mitochondrial dynamics via ERK/Drp1 pathway

Cardiovascular Diabetology, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 20, 2025

Increasing evidence highlights the critical role of Piezo1 in cardiovascular diseases, with its expression upregulated diabetic heart. However, involvement pathogenesis cardiomyopathy (DCM) remains unclear. This study aims to elucidate regulatory mitochondrial dynamics within context DCM and investigate underlying mechanisms. We constructed cardiac-specific knockout (Piezo1∆Myh6) mice. Type 1 diabetes was induced using streptozotocin (STZ) injection while type 2 established through a high-fat diet combined STZ. Echocardiography assessed left ventricular function, histological evaluations used HE Masson staining examine cardiac pathology Piezo1fl/fl controls, Piezo1∆Myh6 Mitochondrial function including oxygen species level, morphology, respiration rate were also assessed. Our findings revealed that myocardium mice high-glucose-treated cells. Cardiac-specific improved dysfunction ameliorated fibrosis Moreover, deficiency attenuated impairment. exhibited increased calpain activity excessive fission mediated by Drp1 obvious reduced fusion; however, restored levels dysfunction. These observations corroborated H9C2 cells neonatal mouse cardiomyocytes. phosphorylation ERK1/2 vivo vitro. or treatment inhibitor function. provides first is elevated modulation dynamics, which reversed deficiency. Thus, inhibition may provide promising therapeutic strategy for DCM. In cardiomyocytes mice, Ca2+ entry upregulates activity, phosphorylated level Drp1. Therefore, shown hearts. Whereas, cardiomyocyte-specific alleviates

Language: Английский

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Methylophiopogonanone A alleviates diabetic cardiomyopathy via inhibiting JNK1 signaling

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111762 - 111762

Published: March 1, 2025

Language: Английский

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Traditional Chinese medicine in the prevention of diabetes mellitus and cardiovascular complications: mechanisms and therapeutic approaches

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 11, 2025

Diabetes mellitus (DM) is a chronic endocrine and metabolic disorder characterized by persistent hyperglycemia that poses serious threats to human health quality of life. The morbidity, disability, mortality rates cardiovascular complications stemming from are primary factors affecting the lifespan patients with diabetes. Currently, there no cure for DM. Standard biomedical treatments mostly control symptoms using insulin injections or oral hypoglycemic drugs. Although effect standard therapy remarkable, its long-term use prone toxic side effects. Numerous studies have recently found Traditional Chinese Medicine (TCM) has strong advantages in prevention treatment DM (DACC). collection, processing, preparation clinical TCM guided theory follow “holistic concept.” Multiple components, pathways, targets form basis treating multiple parts organs body simultaneously. mainly derived natural medicines their processed products fewer clinically used as compound prescriptions, botanical drugs, monomers. TCM, either independently combination treatments, shown unique therapeutic advantages. This review aimed explore reported mechanisms action DACC. These findings will aid optimization current formation schedule integrated treatments.

Language: Английский

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Impact of DPP-4 Inhibitors in Patients with Diabetes Mellitus and Heart Failure: An In-Depth Review

Medicina, Journal Year: 2024, Volume and Issue: 60(12), P. 1986 - 1986

Published: Dec. 2, 2024

The increasing prevalence of both type 2 diabetes mellitus and heart failure has underscored the urgent need for optimized therapeutic strategies that address complex interplay between these conditions. Dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a popular class glucose-lowering agents due to their favorable glycemic effects, safety profile, potential cardiovascular benefits. However, impact DPP-4 on outcomes in patients with remains contentious, conflicting evidence from clinical trials observational studies. This review critically examines current use coexisting failure, focusing pharmacodynamics, safety, efficacy outcomes. We explore physiological mechanisms by which may influence risk, including modulation inflammation, oxidative stress, myocardial fibrosis. Clinical such SAVOR-TIMI 53, EXAMINE, TECOS are evaluated provide comprehensive analysis inhibitors' effects hospitalization mortality, events diabetic patients. While some suggest an increased risk HF hospitalizations specific (e.g., saxagliptin), others report neutral raising questions about versus individual drug characteristics within this group. Additionally, we discrepancies related patient demographics, phenotype, comorbid conditions risk-benefit profile. Comparative insights into alternative therapies SGLT2 GLP-1 receptor agonists also provided, highlighting implications treatment selection high-risk population. In summary, synthesizes available aiming guide clinicians making informed decisions. remain viable option management, caution is warranted advanced future research essential refine patient-specific guidelines.

Language: Английский

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Therapeutic potential of finerenone for diabetic cardiomyopathy: focus on the mechanisms

Diabetology & Metabolic Syndrome, Journal Year: 2024, Volume and Issue: 16(1)

Published: Sept. 18, 2024

Language: Английский

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The role of NF-κB in diabetic cardiomyopathy

All Life, Journal Year: 2024, Volume and Issue: 17(1)

Published: Sept. 5, 2024

Language: Английский

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HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFpEF): TREATMENT OPTIONS AND PATIENT OUTCOMES

Journal of Population Therapeutics and Clinical Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 14, 2024

Hu et al specified that HFpEF is undoubtedly a major as well diverse structural type of heart failure affecting nearly half the new patients identified globally. Compared to HFrEF, similar situation observed in where underlying mechanisms disease are broader and it extremely difficult manage disorder. This study found that, despite optimal medical therapy, with had marked symptom burden, high hospitalization rate, reduced health-related quality life, indicating need for better therapeutic management strategies. The systematic review current treatment diagnosed will focus on effectiveness treatments. In this regard, aims determine knowledge gaps evident within available literature proposals subsequent clinical investigations. search incorporated databases PubMed, Cochrane Library, Embase, Web Science, adhering PRISMA protocol. Article inclusion was guided by specific conditions namely, trials, observation studies, systemic reviews comparing treatments HFpEF. Data extraction assessment were performed using standard tools made very reliable valid. Overall, 45 closed trials met eligibility criterion. Previous pharmacological including ARNIs, SGLT2i MRAs modest effect decreasing CV hospitalizations but neutral small all-cause mortality. Frequent devices such lifestyle changes exercise protocols seen upgrade functional ability besides increasing life However, none these highly effective, always necessitating combination individualized approach. conclusion, therapy presents itself several options have shown promising results complexity disorder due wide divergence its presentation. These suggest pharmacotherapy should be further complemented modifications improve functioning patients. More work has done precisely define individual approaches addressing heterogeneous pathophysiology set clear recommendations.

Language: Английский

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Myocardial Fibrosis in Diabetic Cardiomyopathy: Mechanisms, Implications, and Therapeutic Perspectives

Current Problems in Cardiology, Journal Year: 2024, Volume and Issue: unknown, P. 102976 - 102976

Published: Dec. 1, 2024

Language: Английский

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