ArticleNature medicine2017
Pyruvate kinase M2 activation may protect against the progression of diabetic glomerular pathology and mitochondrial dysfunction.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 303 papers.
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303 citing papers in PubMed, 484 citations in OpenAlex.
- Irbesartan treatment does not influence plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3-deoxyglucosone in participants with type 2 diabetes and microalbuminuria: An IRMA2 sub-study.Diabetic medicine : a journal of the British Diabetic Association · 2021Trial
- Targeting mitochondrial quality control in diabetic kidney disease: emerging therapeutic opportunities.Renal failure · 2026Review
- Nanotechnology-mediated podocyte injury repair: mechanistic exploration and therapeutic prospects.Renal failure · 2026Review
- Inhibition of Hexokinase 2 Undermines Cartilage Health and Accelerates Osteoarthritis.Cartilage · 2026Article
- Arachidonic Acid Disrupts PKM2-Linked Glycolysis-Related Metabolism and Exacerbates PAN-Induced Podocyte Injury.Journal of cellular and molecular medicine · 2026Article
- Symmetry-guided fusion converts weak liver pyruvate kinase inhibitors into potent allosteric activators.RSC medicinal chemistry · 2026Article
- Glyoxalase 1 loss reduces fatty liver but impairs glucose handling in male mice.Physiological reports · 2026Article
- Trained immunity: New insights into pathogenesis and therapeutic targets in diabetes and diabetic complications.Genes & diseases · 2026Review
- Natural products modulate renal metabolic reprogramming in diabetic kidney disease.Journal of translational internal medicine · 2026Article
- Photobiomodulation-reprogrammed extracellular vesicles deliveredActa pharmaceutica Sinica. B · 2026Article
- Article
- Advances in understanding the NLRP3 inflammasome‑mediated mechanisms and therapeutic targets in diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- FBP1 Is Associated with Attenuated Mitochondrial Injury in Renal Tubular Epithelial Cells of Diabetic Kidney Disease via Modulation of Lactate Metabolism.International journal of molecular sciences · 2026Article
- Molecular mechanisms and novel therapeutic targets of diabetic kidney disease.Chinese medical journal · 2026Review
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- Genetically encoded manipulation of ATP/ADP ratio in human cells uncovers proteomic and physiological signatures of energy stress.Cell chemical biology · 2026Article
- Research progress in single‑cell omics technologies for kidney disease (Review).International journal of molecular medicine · 2026Review
- Spatial metabolomics: A new tool for unravelling the metabolic disorders and heterogeneity in diabetic kidney disease (Review).International journal of molecular medicine · 2026Review
- Dimeric PKM2 in chondrocytes impairs mitochondrial homeostasis in osteoarthritis.Cell death & disease · 2026Article
- Role of PKM2 Tetramer in Modulating Endothelial Mitochondrial Dysfunction in a Rat Model of Chronic Thromboembolic Pulmonary Hypertension.Physiological research · 2026Article
243 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 9 institutions in 4 countries.
Funding
Abstract
Diabetic nephropathy (DN) is a major cause of end-stage renal disease, and therapeutic options for preventing its progression are limited. To identify novel therapeutic strategies, we studied protective factors for DN using proteomics on glomeruli from individuals with extreme duration of diabetes (ł50 years) without DN and those with histologic signs of DN. Enzymes in the glycolytic, sorbitol, methylglyoxal and mitochondrial pathways were elevated in individuals without DN. In particular, pyruvate kinase M2 (PKM2) expression and activity were upregulated. Mechanistically, we showed that hyperglycemia and diabetes decreased PKM2 tetramer formation and activity by sulfenylation in mouse glomeruli and cultured podocytes. Pkm-knockdown immortalized mouse podocytes had higher levels of toxic glucose metabolites, mitochondrial dysfunction and apoptosis. Podocyte-specific Pkm2-knockout (KO) mice with diabetes developed worse albuminuria and glomerular pathology. Conversely, we found that pharmacological activation of PKM2 by a small-molecule PKM2 activator, TEPP-46, reversed hyperglycemia-induced elevation in toxic glucose metabolites and mitochondrial dysfunction, partially by increasing glycolytic flux and PGC-1α mRNA in cultured podocytes. In intervention studies using DBA2/J and Nos3 (eNos) KO mouse models of diabetes, TEPP-46 treatment reversed metabolic abnormalities, mitochondrial dysfunction and kidney pathology. Thus, PKM2 activation may protect against DN by increasing glucose metabolic flux, inhibiting the production of toxic glucose metabolites and inducing mitochondrial biogenesis to restore mitochondrial function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.