ArticleDiabetologia2020
Dimethyl-2-oxoglutarate improves redox balance and mitochondrial function in muscle pericytes of individuals with diabetes mellitus.
Article in Diabetologia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Distinct immunometabolic signatures in peripheral blood mononuclear cells are linked to systemic inflammation in type 2 diabetes and diabetic kidney disease.Molecular biomedicine · 2026Article
- Mechanisms of Impaired Skeletal Muscle Regeneration and Therapeutic Approaches in Aging and Chronic Disease.Pharmaceuticals (Basel, Switzerland) · 2026Review
- TET1 Protects the Lungs from Diesel Exhaust Particle-Induced Inflammation and Abnormal Function.Research square · 2026Article
- The stem cell within the vessel wall: multipotent pericytes modulating β-cell function and diabetic complications.Stem cell research & therapy · 2025Review
- Targeted Delivery of α-ketoglutarate to Macrophages in Bone: A Novel Therapeutic Strategy for Improving Fracture Healing in Type 2 Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- [Latest Findings on the Role of α-Ketoglutarate in Metabolic Syndrome].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Review
- MuSCs and IPCs: roles in skeletal muscle homeostasis, aging and injury.Cellular and molecular life sciences : CMLS · 2024Review
- Engineered Extracellular Vesicles Derived from Dermal Fibroblasts Attenuate Inflammation in a Murine Model of Acute Lung Injury.Advanced materials (Deerfield Beach, Fla.) · 2023Article
- Gene therapy targeting inflammatory pericytes corrects angiopathy during diabetic wound healing.Frontiers in immunology · 2022Article
- mTOR/α-ketoglutarate-mediated signaling pathways in the context of brain neurodegeneration and neuroprotection.BBA advances · 2022Article
- Cell Therapy for Critical Limb Ischemia: Advantages, Limitations, and New Perspectives for Treatment of Patients with Critical Diabetic Vasculopathy.Current diabetes reports · 2021Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
aims/hypothesisTreatment of vascular complications of diabetes remains inadequate. We reported that muscle pericytes (MPs) from limb muscles of vascular patients with diabetes mellitus display elevated levels of oxidative stress causing a dysfunctional phenotype. Here, we investigated whether treatment with dimethyl-2-oxoglutarate (DM-2OG), a tricarboxylic acid cycle metabolite with antioxidant properties, can restore a healthy metabolic and functional phenotype.
methodsMPs were isolated from limb muscles of diabetes patients with vascular disease (D-MPs) and from non-diabetic control participants (ND-MPs). Metabolic status was assessed in untreated and DM-2OG-treated (1 mmol/l) cells using an extracellular flux analyser and anion-exchange chromatography-mass spectrometry (IC-MS/MS). Redox status was measured using commercial kits and IC-MS/MS, with antioxidant and metabolic enzyme expression assessed by quantitative RT-PCR and western blotting. Myogenic differentiation and proliferation and pericyte-endothelial interaction were assessed as functional readouts.
resultsD-MPs showed mitochondrial dysfunction, suppressed glycolytic activity and reduced reactive oxygen species-buffering capacity, but no suppression of antioxidant systems when compared with ND-MP controls. DM-2OG supplementation improved redox balance and mitochondrial function, without affecting glycolysis or antioxidant systems. Nonetheless, this was not enough for treated D-MPs to regain the level of proliferation and myogenic differentiation of ND-MPs. Interestingly, DM-2OG exerted a positive effect on pericyte-endothelial cell interaction in the co-culture angiogenesis assay, independent of the diabetic status. CONCLUSIONS/
interpretationThese novel findings support the concept of using DM-2OG supplementation to improve pericyte redox balance and mitochondrial function, while concurrently allowing for enhanced pericyte-endothelial crosstalk. Such effects may help to prevent or slow down vasculopathy in skeletal muscles of people with diabetes. Graphical abstract.
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