ArticleCirculation. Heart failure2015
Activation of Foxo1 by insulin resistance promotes cardiac dysfunction and β-myosin heavy chain gene expression.
Article in Circulation. Heart failure, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 98 citations in OpenAlex.
- Studies of Foxo1 over the Past 25 Years: Mechanisms of Insulin Resistance and Glucose Dysregulation.Cells · 2026Review
- High Glucose Treatment Induces Nuclei Aggregation of Microvascular Endothelial Cells via theArteriosclerosis, thrombosis, and vascular biology · 2025Article
- SGLT2 inhibitor downregulates ANGPTL4 to mitigate pathological aging of cardiomyocytes induced by type 2 diabetes.Cardiovascular diabetology · 2024Article
- In-depth phosphoproteomic profiling of the insulin signaling response in heart tissue and cardiomyocytes unveils canonical and specialized regulation.Cardiovascular diabetology · 2024Article
- Self-assembly of differentiated dental pulp stem cells facilitates spheroid human dental organoid formation and prevascularization.World journal of stem cells · 2024Article
- Article
- Forkhead box O1 transcription factor; a therapeutic target for diabetic cardiomyopathy.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2024Review
- Understanding Diabetic Cardiomyopathy: Insulin Resistance and Beyond.Heart international · 2024Review
- Regulation of Macronutrients in Insulin Resistance and Glucose Homeostasis during Type 2 Diabetes Mellitus.Nutrients · 2023Review
- FOXO1 regulates NLRP3 inflammasome proteins in LPS-induced cardiotoxicity.American journal of translational research · 2023Article
- Heart Failure And Type 2 Diabetes Mellitus: Neurohumoral, Histological And Molecular Interconnections.Current cardiology reviews · 2023Review
- Enhanced Cardiorenal Protective Effects of Combining SGLT2 Inhibition, Endothelin Receptor Antagonism and RAS Blockade in Type 2 Diabetic Mice.International journal of molecular sciences · 2022Article
- Insulin and Insulin-Like Growth Factor 1 Signaling Preserves Sarcomere Integrity in the Adult Heart.Molecular and cellular biology · 2022Article
- Myostatin/AKT/FOXO Signaling Is Altered in Human Non-Ischemic Dilated Cardiomyopathy.Life (Basel, Switzerland) · 2022Article
- An Association between Insulin Resistance and Neurodegeneration in Zebrafish Larval Model (International journal of molecular sciences · 2022Article
- Estrogen Protects Cardiac Function and Energy Metabolism in Dilated Cardiomyopathy Induced by Loss of Cardiac IRS1 and IRS2.Circulation. Heart failure · 2022Article
- Insulin Receptors and Insulin Action in the Heart: The Effects of Left Ventricular Assist Devices.Biomolecules · 2022Review
- Integrating pharmacological evaluation and computational identification for deciphering the action mechanism of Yunpi-Huoxue-Sanjie formula alleviates diabetic cardiomyopathy.Frontiers in pharmacology · 2022Article
- Discovery of Herbacetin as a Novel SGK1 Inhibitor to Alleviate Myocardial Hypertrophy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Calcineurin in the heart: New horizons for an old friend.Cellular signalling · 2021Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundHeart failure is a leading cause of morbidity and mortality in the USA and is closely associated with diabetes mellitus. The molecular link between diabetes mellitus and heart failure is incompletely understood. We recently demonstrated that insulin receptor substrates 1, 2 (IRS1, 2) are key components of insulin signaling and loss of IRS1 and IRS2 mediates insulin resistance, resulting in metabolic dysregulation and heart failure, which is associated with downstream Akt inactivation and in turn activation of the forkhead transcription factor Foxo1. METHODS AND
resultsTo determine the role of Foxo1 in control of heart failure in insulin resistance and diabetes mellitus, we generated mice lacking Foxo1 gene specifically in the heart. Mice lacking both IRS1 and IRS2 in adult hearts exhibited severe heart failure and a remarkable increase in the β-isoform of myosin heavy chain (β-MHC) gene expression, whereas deletion of cardiac Foxo1 gene largely prevented the heart failure and resulted in a decrease in β-MHC expression. The effect of Foxo1 deficiency on rescuing cardiac dysfunction was also observed in db/db mice and high-fat diet mice. Using cultures of primary ventricular cardiomyocytes, we found that Foxo1 interacts with the promoter region of β-MHC and stimulates gene expression, mediating an effect of insulin that suppresses β-MHC expression.
conclusionsOur study suggests that Foxo1 has important roles in promoting diabetic cardiomyopathy and controls β-MHC expression in the development of cardiac dysfunction. Targeting Foxo1 and its regulation will provide novel strategies in preventing metabolic and myocardial dysfunction and influencing MHC plasticity in diabetes mellitus.
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