ArticleJournal of molecular and cellular cardiology2015
Antioxidant treatment normalizes mitochondrial energetics and myocardial insulin sensitivity independently of changes in systemic metabolic homeostasis in a mouse model of the metabolic syndrome.
Article in Journal of molecular and cellular cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Left ventricular vascular and metabolic adaptations to high-intensity interval and moderate intensity continuous training: a randomized trial in healthy middle-aged men.The Journal of physiology · 2016Trial
- Reversing diastolic dysfunction in diabetes: a mitochondrial quality control-centric pharmacological approach.Acta diabetologica · 2026Review
- Dysregulated Redox Signaling and Its Impact on Inflammatory Pathways, Mitochondrial Dysfunction, Autophagy and Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Diabetes cardiomyopathy: targeted regulation of mitochondrial dysfunction and therapeutic potential of plant secondary metabolites.Frontiers in pharmacology · 2024Review
- Cardiac Insulin Resistance in Subjects With Metabolic Syndrome Traits and Early Subclinical Atherosclerosis.Diabetes care · 2023Article
- Depletion of WFS1 compromises mitochondrial function in hiPSC-derived neuronal models of Wolfram syndrome.Stem cell reports · 2023Article
- Article
- The endocrine role of brown adipose tissue: An update on actors and actions.Reviews in endocrine & metabolic disorders · 2022Review
- Metabolic Syndrome Is Associated With Impaired Insulin-Stimulated Myocardial Glucose Metabolic Rate in Individuals With Type 2 Diabetes: A Cardiac DynamicFrontiers in cardiovascular medicine · 2022Article
- Insulin signaling in the heart.American journal of physiology. Endocrinology and metabolism · 2021Review
- Cardiac Energy Metabolism in Heart Failure.Circulation research · 2021Review
- The peroxisomal fatty acid transporter ABCD1/PMP-4 is required in the C. elegans hypodermis for axonal maintenance: A worm model for adrenoleukodystrophy.Free radical biology & medicine · 2020Article
- Mitochondrial Mechanisms in Diabetic Cardiomyopathy.Diabetes & metabolism journal · 2020Review
- Novel Insights Into Molecular Mechanism of Mitochondria in Diabetic Cardiomyopathy.Frontiers in physiology · 2020Review
- Mitochondrial NADAntioxidants & redox signaling · 2019Review
- Heart Failure in Type 2 Diabetes Mellitus.Circulation research · 2019Review
- Biomarkers of Oxidative Stress in Metabolic Syndrome and Associated Diseases.Oxidative medicine and cellular longevity · 2019Review
- Insulin Signaling and Heart Failure.Circulation research · 2016Review
- Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure.Scientific reports · 2015Article
- Time course of cardiometabolic alterations in a high fat high sucrose diet mice model and improvement after GLP-1 analog treatment using multimodal cardiovascular magnetic resonance.Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance · 2015Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Cardiac dysfunction in obesity is associated with mitochondrial dysfunction, oxidative stress and altered insulin sensitivity. Whether oxidative stress directly contributes to myocardial insulin resistance remains to be determined. This study tested the hypothesis that ROS scavenging will improve mitochondrial function and insulin sensitivity in the hearts of rodent models with varying degrees of insulin resistance and hyperglycemia. The catalytic antioxidant MnTBAP was administered to the uncoupling protein-diphtheria toxin A (UCP-DTA) mouse model of insulin resistance (IR) and obesity, at early and late time points in the evolution of IR, and to db/db mice with severe obesity and type-two diabetes. Mitochondrial function was measured in saponin-permeabilized cardiac fibers. Aconitase activity and hydrogen peroxide emission were measured in isolated mitochondria. Insulin-stimulated glucose oxidation, glycolysis and fatty acid oxidation rates were measured in isolated working hearts, and 2-deoxyglucose uptake was measured in isolated cardiomyocytes. Four weeks of MnTBAP attenuated glucose intolerance in 13-week-old UCP-DTA mice but was without effect in 24-week-old UCP-DTA mice and in db/db mice. Despite the absence of improvement in the systemic metabolic milieu, MnTBAP reversed cardiac mitochondrial oxidative stress and improved mitochondrial bioenergetics by increasing ATP generation and reducing mitochondrial uncoupling in all models. MnTBAP also improved myocardial insulin mediated glucose metabolism in 13 and 24-week-old UCP-DTA mice. Pharmacological ROS scavenging improves myocardial energy metabolism and insulin responsiveness in obesity and type 2 diabetes via direct effects that might be independent of changes in systemic metabolism.
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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.