ArticlePloS one2016
Oxamate Improves Glycemic Control and Insulin Sensitivity via Inhibition of Tissue Lactate Production in db/db Mice.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
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- Eliminate pneumococcal colonization by targeting intracellular acidification that promotes H2O2 production to enhance bacterial survival.PLoS pathogens · 2026Article
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- LDHA induces beta cell dedifferentiation in diabetes through metabolic and epigenetic reprogramming.Diabetologia · 2026Article
- Glycolytic heterogeneity drives metabolic-targeted therapy in pancreatic ductal adenocarcinoma.Signal transduction and targeted therapy · 2026Article
- Identification of potential shared core biomarkers in type 2 diabetes and sarcopenia.Scientific reports · 2025Article
- Oxamate suppresses whole-body energy metabolism at rest and during exercise in mice by inhibiting fat oxidation and altering lactate dynamics.Physical activity and nutrition · 2025Article
- Enzymatic post-translational modifications of proteins in chronic kidney disease: mechanisms, regulation, and clinical significance.Frontiers in pharmacology · 2025Review
- Intrathecal lactate dehydrogenase A inhibitors FX11 and oxamate alleviate chronic constriction injury-induced nociceptive sensitization through neuroinflammation and angiogenesis.The journal of headache and pain · 2024Article
- Longitudinal changes of serum metabolomic profile after laparoscopic sleeve gastrectomy in obesity.Endocrine connections · 2024Article
- Article
- The effect of lactate dehydrogenase inhibitors on proliferation, motility and invasion of breast cancer cellsMolecular medicine reports · 2024Article
- LDH-A Inhibitor as a Remedy to Potentiate the Anticancer Effect of Docetaxel in Prostate Cancer.Journal of Cancer · 2024Article
- Recent Progress in the Development of New Antiepileptic Drugs with Novel Targets.Annals of neurosciences · 2023Review
- Destabilization of β Cell FIT2 by saturated fatty acids alter lipid droplet numbers and contribute to ER stress and diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Transcriptome Analysis Reveal Candidate Genes and Pathways Responses to Lactate Dehydrogenase Inhibition (Oxamate) in Hyperglycemic Human Renal Proximal Epithelial Tubular Cells.Frontiers in endocrinology · 2022Article
- LDHA is enriched in human islet alpha cells and upregulated in type 2 diabetes.Biochemical and biophysical research communications · 2021Article
- Lactate Dehydrogenase Inhibition With Oxamate Exerts Bone Anabolic Effect.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020Article
- Potential therapeutic effect of Moroccan propolis in hyperglycemia, dyslipidemia, and hepatorenal dysfunction in diabetic rats.Iranian journal of basic medical sciences · 2019Article
- Extrinsic and Intrinsic Immunometabolism Converge: Perspectives on Future Research and Therapeutic Development for Obesity.Current obesity reports · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxamate (OXA) is a pyruvate analogue that directly inhibits the lactate dehydrogenase (LDH)-catalyzed conversion process of pyruvate into lactate. Earlier and recent studies have shown elevated blood lactate levels among insulin-resistant and type 2 diabetes subjects and that blood lactate levels independently predicted the development of incident diabetes. To explore the potential of OXA in the treatment of diabetes, db/db mice were treated with OXA in vivo. Treatment of OXA (350-750 mg/kg of body weight) for 12 weeks was shown to decrease body weight gain and blood glucose and HbA1c levels and improve insulin secretion, the morphology of pancreatic islets, and insulin sensitivity in db/db mice. Meanwhile, OXA reduced the lactate production of adipose tissue and skeletal muscle and serum lactate levels and decreased serum levels of TG, FFA, CRP, IL-6, and TNF-α in db/db mice. The PCR array showed that OXA downregulated the expression of Tnf, Il6, leptin, Cxcr3, Map2k1, and Ikbkb, and upregulated the expression of Irs2, Nfkbia, and Pde3b in the skeletal muscle of db/db mice. Interestingly, LDH-A expression increased in the islet cells of db/db mice, and both treatment of OXA and pioglitazone decreased LDH-A expression, which might be related to the improvement of insulin secretion. Taken together, increased lactate production of adipose tissue and skeletal muscle may be at least partially responsible for insulin resistance and diabetes in db/db mice. OXA improved glycemic control and insulin sensitivity in db/db mice primarily via inhibition of tissue lactate production. Oxamic acid derivatives may be a potential drug for the treatment of type 2 diabetes.
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