ArticleJournal of cachexia, sarcopenia and muscle2021
Mitochondrial dysfunction in skeletal muscle contributes to the development of acute insulin resistance in mice.
Article in Journal of cachexia, sarcopenia and muscle, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- Myokines and mitochondrial function in cardiometabolic diseases.Journal of physiology and biochemistry · 2026Review
- Diabetes-TyG interaction and mortality in critical cerebrovascular disease: a retrospective cohort study.Scientific reports · 2026Article
- Modulation of Microbiome-Mitochondria Axis as a Novel Approach for Treatment of Obesity: A Scoping Review.Medical sciences (Basel, Switzerland) · 2026Article
- Insulin resistance: mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Perfluorooctane sulfonic acid (PFOS) perturbs skeletal muscle oxidative phosphorylation by a different mechanism than liver.Chemosphere · 2026Article
- Niclosamide extends health span and reduces frailty by ameliorating mTORC1 hyperactivation in aging models.Journal of advanced research · 2026Article
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- Integrated transcriptomics unveils mitochondrial oxidative phosphorylation dysfunction as a shared mechanism in sarcopenia and obesity.Scientific reports · 2025Article
- Skeletal muscle atrophy and dysfunction in obesity and type-2 diabetes mellitus: Myocellular mechanisms involved.Reviews in endocrine & metabolic disorders · 2025Review
- Intermuscular Adipose Tissue in CKD: A Window into Muscle Quality and Health?Clinical journal of the American Society of Nephrology : CJASN · 2025Review
- Elevated levels of S100A8 and S100A9 exacerbate muscle mitochondrial fragmentation in sepsis-induced muscle atrophy.Communications biology · 2025Article
- Metabolic and molecular regulation in skeletal muscle dysfunction and regeneration.Frontiers in cell and developmental biology · 2025Review
- Mechanisms of insulin resistance in type 1 diabetes mellitus: A case of glucolipotoxicity in skeletal muscle.Journal of cellular physiology · 2024Review
- The effect of low birth weight as an intrauterine exposure on the early onset of sarcopenia through possible molecular pathways.Journal of cachexia, sarcopenia and muscle · 2024Review
- Article
- Review
- Potential regulatory role of PGC-1α within the skeletal muscle during metabolic adaptations in response to high-fat diet feeding in animal models.Pflugers Archiv : European journal of physiology · 2024Review
- High-intensity interval training attenuates impairment in regulatory protein machinery of mitochondrial quality control in skeletal muscle of diet-induced obese mice.Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme · 2024Article
- Inhibition of the skeletal muscle Lands cycle ameliorates weakness induced by physical inactivity.Journal of cachexia, sarcopenia and muscle · 2024Article
- Mitochondrial Dysfunction, Oxidative Stress, and Inter-Organ Miscommunications in T2D Progression.International journal of molecular sciences · 2024Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough mounting evidence indicates that insulin resistance (IR) co-occurs with mitochondrial dysfunction in skeletal muscle, there is no clear causal link between mitochondrial dysfunction and IR pathogenesis. In this study, the exact role of mitochondria in IR development was determined.
methodsSix-week-old C57BL/6 mice were fed a high-fat diet for 2 weeks to induce acute IR or for 24 weeks to induce chronic IR (n = 8 per group). To characterize mitochondrial function, we measured citrate synthase activity, ATP content, mitochondrial DNA (mtDNA) content, and oxygen consumption rate in gastrocnemius and liver tissues. We intraperitoneally administered mitochondrial division inhibitor 1 (mdivi-1) to mice with acute IR and measured mitochondrial adaptive responses such as mitophagy, mitochondrial unfolded protein response (UPRmt), and oxidative stress (n = 6 per group).
resultsAcute IR occurred coincidently with impaired mitochondrial function, including reduced citrate synthase activity (-37.8%, P < 0.01), ATP production (-88.0%, P < 0.01), mtDNA (-53.1%, P < 0.01), and mitochondrial respiration (-52.2% for maximal respiration, P < 0.05) in skeletal muscle but not in liver. Administration of mdivi-1 attenuated IR development by increasing mitochondrial function (+58.5% for mtDNA content, P < 0.01; 4.06 ± 0.69 to 5.84 ± 0.95 pmol/min/mg for citrate synthase activity, P < 0.05; 13.06 ± 0.70 to 34.87 ± 0.70 pmol/min/g for maximal respiration, P < 0.001). Western blot analysis showed acute IR resulted in increased autophagy (mitophagy) and UPRmt induction in muscle tissue. This adaptive response was inhibited by mdivi-1, which reduced the mitochondrial oxidative stress of skeletal muscle during acute IR.
conclusionsAcute IR induced mitochondrial oxidative stress that impaired mitochondrial function in skeletal muscle. Improving mitochondrial function has important potential for treating acute IR.
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