ArticleDiabetes2013
Myocardial loss of IRS1 and IRS2 causes heart failure and is controlled by p38α MAPK during insulin resistance.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
107 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.
- The crucial role and mechanism of insulin resistance in metabolic disease.Frontiers in endocrinology · 2023Pooled it
- Prognostic Value of Dynamic FDG PET-Derived Myocardial Glucose Metabolism in Ischemic Cardiomyopathy with Supportive External Gene-Expression Analysis.Diagnostics (Basel, Switzerland) · 2026Article
- Article
- Senescence dynamics define therapeutic windows for Duchenne muscular dystrophy in DBA/2-mdx mice.Skeletal muscle · 2026Article
- Targeting Insulin Resistance Through Nutrition: Pathophysiological Insights and Dietary Interventions.Nutrients · 2026Review
- Diabetes and cancer: therapeutic implications.Cardio-oncology (London, England) · 2026Review
- What Is Cardiometabolic HFpEF and How Can We Study it Preclinically?JACC. Basic to translational science · 2025Review
- Relationship of Ageing to Insulin Resistance and Atherosclerosis.Metabolites · 2025Review
- Simultaneous in vivo multi-organ fluxomics reveals divergent metabolic adaptations in liver, heart, and skeletal muscle during obesity.Cell reports · 2025Article
- Empagliflozin in diabetic cardiomyopathy: elucidating mechanisms, therapeutic potentials, and future directions.Molecular biology reports · 2025Review
- Comparison of different insulin resistance surrogates in predicting hyperuricemia in non-diabetic Yi residents in Yunnan Province.Frontiers in endocrinology · 2025Article
- Mechanisms and therapeutics of insulin signaling transduction genes in diabetic cardiomyopathy: a comprehensive updated review.Frontiers in endocrinology · 2025Review
- Multi-omics insights into the pathogenesis of diabetic cardiomyopathy: epigenetic and metabolic profiles.Epigenomics · 2025Article
- Evaluating sex-specific responses to western diet across the lifespan: impact on cardiac function and transcriptomic signatures in C57BL/6J mice at 530 and 640/750 days of age.Cardiovascular diabetology · 2024Article
- The treatment of chronic anemia in heart failure: a global approach.Clinical research in cardiology : official journal of the German Cardiac Society · 2024Review
- Differential gene expression patterns in ST-elevation Myocardial Infarction and Non-ST-elevation Myocardial Infarction.Scientific reports · 2024Article
- Insulin resistance is associated with subclinical myocardial dysfunction and reduced functional capacity in heart failure with preserved ejection fraction.Journal of cardiology · 2024Article
- Diabetes cardiomyopathy: targeted regulation of mitochondrial dysfunction and therapeutic potential of plant secondary metabolites.Frontiers in pharmacology · 2024Review
- Association between METS-IR and heart failure: a cross-sectional study.Frontiers in endocrinology · 2024Article
- Understanding Diabetic Cardiomyopathy: Insulin Resistance and Beyond.Heart international · 2024Review
47 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Cardiac failure is a major cause of death in patients with type 2 diabetes, but the molecular mechanism that links diabetes to heart failure remains unclear. Insulin resistance is a hallmark of type 2 diabetes, and insulin receptor substrates 1 and 2 (IRS1 and IRS2) are the major insulin-signaling components regulating cellular metabolism and survival. To determine the role of IRS1 and IRS2 in the heart and examine whether hyperinsulinemia causes myocardial insulin resistance and cellular dysfunction via IRS1 and IRS2, we generated heart-specific IRS1 and IRS2 gene double-knockout (H-DKO) mice and liver-specific IRS1 and IRS2 double-knockout (L-DKO) mice. H-DKO mice had reduced ventricular mass; developed cardiac apoptosis, fibrosis, and failure; and showed diminished Akt→forkhead box class O-1 signaling that was accompanied by impaired cardiac metabolic gene expression and reduced ATP content. L-DKO mice had decreased cardiac IRS1 and IRS2 proteins and exhibited features of heart failure, with impaired cardiac energy metabolism gene expression and activation of p38α mitogen-activated protein kinase (p38). Using neonatal rat ventricular cardiomyocytes, we further found that chronic insulin exposure reduced IRS1 and IRS2 proteins and prevented insulin action through activation of p38, revealing a fundamental mechanism of cardiac dysfunction during insulin resistance and type 2 diabetes.
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What OpenQuestion holds
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.