ArticleThe Journal of clinical investigation2013
Insulin receptor substrate signaling suppresses neonatal autophagy in the heart.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 114 citations in OpenAlex.
- Mechanobiology of the diabetic cardiomyocyte: insulin signaling, titin elasticity, and multiscale mechanical dysfunction.Biophysical reviews · 2026Review
- Protective Factors and the Pathogenesis of Complications in Diabetes.Endocrine reviews · 2024Review
- Control of NADThe EMBO journal · 2024Article
- Cross Talks between CNS and CVS Diseases: An Alliance to Annihilate.Current cardiology reviews · 2024Review
- Extracellular matrix remodelling in obesity and metabolic disorders.Life metabolism · 2023Article
- Insulin signaling is critical for sinoatrial node maintenance and function.Experimental & molecular medicine · 2023Article
- Autophagy, innate immunity, and cardiac disease.Frontiers in cell and developmental biology · 2023Review
- Vitamin A preserves cardiac energetic gene expression in a murine model of diet-induced obesity.American journal of physiology. Heart and circulatory physiology · 2022Article
- Insulin and Insulin-Like Growth Factor 1 Signaling Preserves Sarcomere Integrity in the Adult Heart.Molecular and cellular biology · 2022Article
- Mitochondrial Quality Control Mechanisms during Diabetic Cardiomyopathy.JMA journal · 2022Review
- Animal Models of Dysregulated Cardiac Metabolism.Circulation research · 2022Review
- New insights into the role of melatonin in diabetic cardiomyopathy.Pharmacology research & perspectives · 2022Review
- Understanding diabetes-induced cardiomyopathy from the perspective of renin angiotensin aldosterone system.Pflugers Archiv : European journal of physiology · 2022Review
- Review
- Insulin signaling in the heart.American journal of physiology. Endocrinology and metabolism · 2021Review
- Mitochondrial Bioenergetics and Dynamism in the Failing Heart.Life (Basel, Switzerland) · 2021Review
- Energy metabolism disorders and potential therapeutic drugs in heart failure.Acta pharmaceutica Sinica. B · 2021Review
- Mitophagy in Diabetic Cardiomyopathy: Roles and Mechanisms.Frontiers in cell and developmental biology · 2021Review
- Targeting Ferroptosis to Treat Cardiovascular Diseases: A New Continent to Be Explored.Frontiers in cell and developmental biology · 2021Review
- The Diabetic Cardiomyopathy: The Contributing Pathophysiological Mechanisms.Frontiers in medicine · 2021Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
The induction of autophagy in the mammalian heart during the perinatal period is an essential adaptation required to survive early neonatal starvation; however, the mechanisms that mediate autophagy suppression once feeding is established are not known. Insulin signaling in the heart is transduced via insulin and IGF-1 receptors (IGF-1Rs). We disrupted insulin and IGF-1R signaling by generating mice with combined cardiomyocyte-specific deletion of Irs1 and Irs2. Here we show that loss of IRS signaling prevented the physiological suppression of autophagy that normally parallels the postnatal increase in circulating insulin. This resulted in unrestrained autophagy in cardiomyocytes, which contributed to myocyte loss, heart failure, and premature death. This process was ameliorated either by activation of mTOR with aa supplementation or by genetic suppression of autophagic activation. Loss of IRS1 and IRS2 signaling also increased apoptosis and precipitated mitochondrial dysfunction, which were not reduced when autophagic flux was normalized. Together, these data indicate that in addition to prosurvival signaling, insulin action in early life mediates the physiological postnatal suppression of autophagy, thereby linking nutrient sensing to postnatal cardiac development.
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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.