ArticleJCI insight2020
Insulin receptor substrates differentially exacerbate insulin-mediated left ventricular remodeling.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Insights and perspectives into the etiology of TKI-induced cardiotoxicity.ASPET discovery · 2026Article
- Article
- Protective Factors and the Pathogenesis of Complications in Diabetes.Endocrine reviews · 2024Review
- Hypoxia Attenuates Pressure Overload-Induced Heart Failure.Journal of the American Heart Association · 2024Article
- Conserved chamber-specific polyploidy maintains heart function in Drosophila.Development (Cambridge, England) · 2023Article
- Exercise, exerkines, and cardiometabolic health: from individual players to a team sport.The Journal of clinical investigation · 2023Review
- Dietary essential amino acids for the treatment of heart failure with reduced ejection fraction.Cardiovascular research · 2023Article
- Diabetic vascular diseases: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- Emerging Therapy for Diabetic Cardiomyopathy: From Molecular Mechanism to Clinical Practice.Biomedicines · 2023Review
- Driving force of deteriorated cellular environment in heart failure: Metabolic remodeling.Clinics (Sao Paulo, Brazil) · 2023Review
- Insulin and Insulin-Like Growth Factor 1 Signaling Preserves Sarcomere Integrity in the Adult Heart.Molecular and cellular biology · 2022Article
- Transcriptomal Insights of Heart Failure from Normality to Recovery.Biomolecules · 2022Article
- Insulin Receptors and Insulin Action in the Heart: The Effects of Left Ventricular Assist Devices.Biomolecules · 2022Review
- Insulin action at a molecular level - 100 years of progress.Molecular metabolism · 2021Review
- Insulin signaling in the heart.American journal of physiology. Endocrinology and metabolism · 2021Review
- Cardiac Energy Metabolism in Heart Failure.Circulation research · 2021Review
- It takes a village: lessons from collaborative science.The Journal of clinical investigation · 2021Article
- Echocardiographic parameters according to insulin dose in young patients affected by type 1 diabetes.PloS one · 2020Observational
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
Pressure overload (PO) cardiac hypertrophy and heart failure are associated with generalized insulin resistance and hyperinsulinemia, which may exacerbate left ventricular (LV) remodeling. While PO activates insulin receptor tyrosine kinase activity that is transduced by insulin receptor substrate 1 (IRS1), the present study tested the hypothesis that IRS1 and IRS2 have divergent effects on PO-induced LV remodeling. We therefore subjected mice with cardiomyocyte-restricted deficiency of IRS1 (CIRS1KO) or IRS2 (CIRS2KO) to PO induced by transverse aortic constriction (TAC). In WT mice, TAC-induced LV hypertrophy was associated with hyperactivation of IRS1 and Akt1, but not IRS2 and Akt2. CIRS1KO hearts were resistant to cardiac hypertrophy and heart failure in concert with attenuated Akt1 activation. In contrast, CIRS2KO hearts following TAC developed more severe LV dysfunction than WT controls, and this was prevented by haploinsufficiency of Akt1. Failing human hearts exhibited isoform-specific IRS1 and Akt1 activation, while IRS2 and Akt2 activation were unchanged. Kinomic profiling identified IRS1 as a potential regulator of cardioprotective protein kinase G-mediated signaling. In addition, gene expression profiling revealed that IRS1 signaling may promote a proinflammatory response following PO. Together, these data identify IRS1 and Akt1 as critical signaling nodes that mediate LV remodeling in both mice and humans.
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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.