ArticleDiabetes2010
Increased reactive oxygen species production and lower abundance of complex I subunits and carnitine palmitoyltransferase 1B protein despite normal mitochondrial respiration in insulin-resistant human skeletal muscle.
Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 1 of them a synthesis that pooled it.
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Who cites it
101 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.
- Common variation in oxidative phosphorylation genes is not a major cause of insulin resistance or type 2 diabetes.Diabetologia · 2012Pooled it
- Skeletal muscle hypertrophy and enhanced mitochondrial bioenergetics following electrical stimulation exercises in spinal cord injury: a randomized clinical trial.European journal of applied physiology · 2025Trial
- Markers of branched-chain amino acid catabolism are not affected by exercise training in pregnant women with obesity.Journal of applied physiology (Bethesda, Md. : 1985) · 2021Trial
- Four days of bed rest increases intrinsic mitochondrial respiratory capacity in young healthy males.Physiological reports · 2018Trial
- The effects of 2 weeks of statin treatment on mitochondrial respiratory capacity in middle-aged males: the LIFESTAT study.European journal of clinical pharmacology · 2017Trial
- Defects in mitochondrial efficiency and H2O2 emissions in obese women are restored to a lean phenotype with aerobic exercise training.Diabetes · 2015Trial
- Trial
- Effect of short-term thyroxine administration on energy metabolism and mitochondrial efficiency in humans.PloS one · 2012Trial
- Myokines and mitochondrial function in cardiometabolic diseases.Journal of physiology and biochemistry · 2026Review
- Kidney mitochondrial complex I dysfunction in a juvenile rat model of diabetic ketoacidosis.Pediatric research · 2026Article
- The emerging role of branched-chain amino acid metabolism in obesity.International journal of obesity (2005) · 2026Review
- Epigenetic modification increases skeletal muscle resilience to metabolic stress.Nature metabolism · 2025Article
- Kdm2a inhibition in skeletal muscle improves metabolic flexibility in obesity.Nature metabolism · 2025Article
- Association between protein undernutrition and diabetes: Molecular implications in the reduction of insulin secretion.Reviews in endocrine & metabolic disorders · 2024Review
- Association of Elevated Serum Branched-chain Amino Acid Levels With Longitudinal Skeletal Muscle Loss.Journal of the Endocrine Society · 2024Article
- The Physiological and Pathological Role of Acyl-CoA Oxidation.International journal of molecular sciences · 2023Review
- Excessive Gestational Weight Gain Alters DNA Methylation and Influences Foetal and Neonatal Body Composition.Epigenomes · 2023Article
- Low Protein Programming Causes Increased Mitochondrial Fusion and Decreased Oxygen Consumption in the Hepatocytes of Female Rats.Nutrients · 2023Article
- Fuel Selection in Skeletal Muscle Exercising at Low Intensity; Reliance on Carbohydrate in Very Sedentary Individuals.Metabolic syndrome and related disorders · 2023Article
- Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 1 institution in 2 countries.
Funding
Abstract
objectiveThe contribution of mitochondrial dysfunction to skeletal muscle insulin resistance remains elusive. Comparative proteomics are being applied to generate new hypotheses in human biology and were applied here to isolated mitochondria to identify novel changes in mitochondrial protein abundance present in insulin-resistant muscle. RESEARCH DESIGN AND
methodsMitochondria were isolated from vastus lateralis muscle from lean and insulin-sensitive individuals and from obese and insulin-resistant individuals who were otherwise healthy. Respiration and reactive oxygen species (ROS) production rates were measured in vitro. Relative abundances of proteins detected by mass spectrometry were determined using a normalized spectral abundance factor method.
resultsNADH- and FADH(2)-linked maximal respiration rates were similar between lean and obese individuals. Rates of pyruvate and palmitoyl-DL-carnitine (both including malate) ROS production were significantly higher in obesity. Mitochondria from obese individuals maintained higher (more negative) extramitochondrial ATP free energy at low metabolic flux, suggesting that stronger mitochondrial thermodynamic driving forces may underlie the higher ROS production. Tandem mass spectrometry identified protein abundance differences per mitochondrial mass in insulin resistance, including lower abundance of complex I subunits and enzymes involved in the oxidation of branched-chain amino acids (BCAA) and fatty acids (e.g., carnitine palmitoyltransferase 1B).
conclusionsWe provide data suggesting normal oxidative capacity of mitochondria in insulin-resistant skeletal muscle in parallel with high rates of ROS production. Furthermore, we show specific abundance differences in proteins involved in fat and BCAA oxidation that might contribute to the accumulation of lipid and BCAA frequently associated with the pathogenesis of insulin resistance.
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Registered trials
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.