ArticleCardiovascular diabetology2024
MCT4-dependent lactate transport: a novel mechanism for cardiac energy metabolism injury and inflammation in type 2 diabetes mellitus.
Article in Cardiovascular diabetology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- The lactate-lactylation axis in renal fibrosis: potential mechanisms in diabetic kidney disease.Annals of medicine · 2025Pooled it
- Review
- The Trajectory of Epigenetic Chromatin Remodeling in Cardiometabolic Disease and its Therapeutic Implications.Journal of cardiovascular translational research · 2026Review
- Lactylation: A central metabolic-epigenetic driver of sepsis-associated acute kidney injury.Molecular biology reports · 2026Review
- Metabolite and nutrient regulation of macrophages in obesity and metabolic disease.Nature reviews. Immunology · 2026Review
- Mechanistic Studies of Lactate in Heart Failure: From Metabolic Biomarker to Therapeutic Target.Reviews in cardiovascular medicine · 2026Review
- Mycobacterium tuberculosis MEM39 (Rv1977) hijacks host aldolase A (ALDOA) to subvert immunometabolism to facilitate bacterial intracellular survival.Cellular & molecular immunology · 2026Article
- Lactate as a Cardiovascular Exerkine: Mechanisms, Signaling Pathways, and Clinical Implications.Biomolecules · 2026Review
- Glycolytic lactylation modulates cell death decisions in diabetic kidney disease: Metabolic‑epigenetic interplay between ferroptosis and autophagy in fibrotic remodeling (Review).International journal of molecular medicine · 2026Review
- Keratin 18 functions as a lactyltransferase to trigger necroptosis in diabetic kidney disease by modulating Fas transcription.Experimental & molecular medicine · 2026Article
- Lactylation enzymes in cancer: Mechanisms and novel therapeutic approaches (Review).Oncology letters · 2026Review
- Lactylation: a promising target for musculoskeletal disorders via interactions with chronic inflammation.Journal of advanced research · 2026Review
- The Role of the Pentose Phosphate Pathway in Cardiovascular Diseases.Cardiovascular drugs and therapy · 2026Review
- Lactylation in cardiac repair: Nexus and therapeutic opportunity.Journal of molecular and cellular cardiology plus · 2026Review
- Lactate and lactylation: mechanisms, function, diseases, and therapeutic targets.Molecular biomedicine · 2026Review
- Lactylation-regulated ferroptosis: mechanisms, disease associations, and therapeutic strategies.Archives of pharmacal research · 2026Review
- Identification and validation of lactylation-related diagnostic biomarkers for type 2 diabetes by WGCNA.Journal of clinical biochemistry and nutrition · 2026Article
- TrxR2 Lactylation Facilitates Mitochondrial Protection and Endothelial Ferroptosis Resistance in Diabetic Cardiomyopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- NPM3 functions as a lactyltransferase to promote necroptosis in male diabetic cardiomyopathy mice models via FASN transcription modulation.Nature communications · 2026Article
- AARS1-mediated lactylation of H3K18 and STAT1 promotes ferroptosis in diabetic nephropathy.Cell death and differentiation · 2026Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Diabetic cardiomyopathy (DCM) is a major contributor to mortality in diabetic patients, characterized by a multifaceted pathogenesis and limited therapeutic options. While lactate, a byproduct of glycolysis, is known to be significantly elevated in type 2 diabetes, its specific role in DCM remains uncertain. This study reveals an abnormal upregulation of monocarboxylate transporter 4 (MCT4) on the plasma membrane of cardiomyocytes in type 2 diabetes, leading to excessive lactate efflux from these cells. The disruption in lactate transport homeostasis perturbs the intracellular lactate-pyruvate balance in cardiomyocytes, resulting in oxidative stress and inflammatory responses that exacerbate myocardial damage. Additionally, our findings suggest increased lactate efflux augments histone H4K12 lactylation in macrophages, facilitating inflammatory infiltration within the microenvironment. In vivo experiments have demonstrated that inhibiting MCT4 effectively alleviates myocardial oxidative stress and pathological damage, reduces inflammatory macrophage infiltration, and enhances cardiac function in type 2 diabetic mice. Furthermore, a clinical prediction model has been established, demonstrating a notable association between peripheral blood lactate levels and diastolic dysfunction in individuals with type 2 diabetes. This underscores the potential of lactate as a prognostic biomarker for DCM. Ultimately, our findings highlight the pivotal involvement of MCT4 in the dysregulation of cardiac energy metabolism and macrophage-mediated inflammation in type 2 diabetes. These insights offer novel perspectives on the pathogenesis of DCM and pave the way for the development of targeted therapeutic strategies against this debilitating condition.
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