ArticleJournal of molecular and cellular cardiology2017
Activation of IGF-1 receptors and Akt signaling by systemic hyperinsulinemia contributes to cardiac hypertrophy but does not regulate cardiac autophagy in obese diabetic mice.
Article in Journal of molecular and cellular cardiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 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
27 citing papers in PubMed, 39 citations in OpenAlex.
- Late-in-life treadmill training mitigates gut microbiome imbalances and cardiovascular disease risk in mice.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- The relationship between IGF-1 and cardiovascular diseases and the potential mediating role of TyG-related index: evidence from a cohort study.BMC cardiovascular disorders · 2026Article
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Review
- Obesity accelerates cardiovascular ageing.European heart journal · 2025Review
- Autophagy in High-Fat Diet and Streptozotocin-Induced Metabolic Cardiomyopathy: Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2025Review
- The Critical Role of Autophagy in the Pathogenesis of Diabetic Osteoporosis: Mechanisms and Therapeutic Measures.Drug design, development and therapy · 2025Review
- Duodenogastric Intussusception in a 14-Week-Old Infant with Donohue Syndrome: Case Study.Case reports in pediatrics · 2023Article
- The complex network of mTOR signalling in the heart.Cardiovascular research · 2022Review
- Relevance of mitochondrial dysfunction in heart disease associated with insulin resistance conditions.Pflugers Archiv : European journal of physiology · 2022Review
- Late-in-life treadmill training rejuvenates autophagy, protein aggregate clearance, and function in mouse hearts.Aging cell · 2021Article
- Obesity cardiomyopathy: evidence, mechanisms, and therapeutic implications.Physiological reviews · 2021Review
- Insulin signaling in the heart.American journal of physiology. Endocrinology and metabolism · 2021Review
- Basic Mechanisms of Diabetic Heart Disease.Circulation research · 2020Review
- Myocardium Metabolism in Physiological and Pathophysiological States: Implications of Epicardial Adipose Tissue and Potential Therapeutic Targets.International journal of molecular sciences · 2020Review
- Echocardiographic parameters according to insulin dose in young patients affected by type 1 diabetes.PloS one · 2020Observational
- Phosphorylation Modifications Regulating Cardiac Protein Quality Control Mechanisms.Frontiers in physiology · 2020Review
- Cellular Protein Quality Control in Diabetic Cardiomyopathy: From Bench to Bedside.Frontiers in cardiovascular medicine · 2020Review
- Suppression of Cardiac Autophagy by Hyperinsulinemia in Insulin Receptor-Deficient Hearts Is Mediated by Insulin-Like Growth Factor Receptor Signaling.Antioxidants & redox signaling · 2019Article
- Autophagy in Adipose Tissue Physiology and Pathophysiology.Antioxidants & redox signaling · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Autophagy plays an important role in the maintenance of normal heart function. However, the role of autophagy in the inulin resistant and diabetic heart is not well understood. Furthermore, the upstream signaling and the downstream targets involved in cardiac autophagy regulation during obesity and type 2 diabetes mellitus (T2DM) are not fully elucidated. The aim of this study was to measure autophagic flux and to dissect the upstream and downstream signaling involved in cardiac autophagy regulation in the hearts of obese T2DM mice. Our study demonstrated that cardiac autophagic flux is suppressed in the heart of obese diabetic (ob/ob) mice due to impaired autophagosome formation. We showed that suppression of autophagy was due to sustained activation of mTOR as we could restore cardiac autophagy by inhibiting mTOR. Moreover, the novel finding of this study is that while IGF-1 receptor-mediated Akt activation contributes to cardiac hypertrophy, it is not involved in mTOR activation and autophagy suppression in obesity and T2DM. In contrast, inhibition of ERK signaling abolished mTOR activation and restored autophagy in the heart of obese diabetic (ob/ob) mice. The study identifies mechanisms regulating cardiac autophagy in obesity and T2DM that are mediated by ERK/mTOR but are distinct from Akt. The findings are of significant importance as they demonstrate for the first time the contribution of IGF-1 receptors (IGF-1R) and Akt signaling in cardiac hypertrophy but not in cardiac autophagy regulation in obesity and T2DM.
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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.