ArticleCirculation research2014
Mutation in the γ2-subunit of AMP-activated protein kinase stimulates cardiomyocyte proliferation and hypertrophy independent of glycogen storage.
Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 79 citations in OpenAlex.
- AMPKγ2-Myosin Interaction: A Glycogen-Independent Trigger for PRKAG2 Cardiomyopathy.Journal of cardiovascular translational research · 2026Article
- AMPKγ2 Regulates Cardiac Hypertrophy and Arrhythmias via Interacting With Myosin.Circulation research · 2026Article
- VCPIP1 drives diabetic cardiomyopathy by deubiquitinating AMPKγ1 and preventing AMPKα-γ subunit assembly in cardiomyocytes.Signal transduction and targeted therapy · 2026Article
- PRKAG2 Cardiomyopathy: A Case-Control Study on the Diagnostic Yield Of Histopathology and Ultrastructural Analysis from Endomyocardial Biopsy.Arquivos brasileiros de cardiologia · 2026Observational
- Mapping DNA methylation to cardiac pathologies induced by beta-adrenergic stimulation in a large panel of mice.Epigenetics · 2025Article
- Empagliflozin enhances metabolic efficiency and improves left ventricular hypertrophy in a hypertrophic cardiomyopathy mouse model.European heart journal · 2025Article
- The role of mechanosignaling in the control of myocardial mass.American journal of physiology. Heart and circulatory physiology · 2025Review
- Isoform-specific roles of AMP-activated protein kinase in cardiac physiology and pathophysiology.Frontiers in cardiovascular medicine · 2025Review
- The metabolic sensor AMPK: Twelve enzymes in one.Molecular metabolism · 2024Review
- Review
- When Paying Attention Pays Back: Missense Mutation c.1006G>A p. (Val336Ile) inInternational journal of molecular sciences · 2024Review
- Fine-tuning AMPK in physiology and disease using point-mutant mouse models.Disease models & mechanisms · 2024Review
- Mechanisms Underlying the Therapeutic Effects of Nicotinamide Mononucleotide in Treating High-fat Diet-induced Hypertrophic Cardiomyopathy based on GEO Datasets, Network Pharmacology, and Molecular Docking.Current pharmaceutical design · 2024Article
- Research Hotspots and Trends in Global Cancer immunometabolism:A Bibliometric Analysis from 2000 to 2023.Journal of multidisciplinary healthcare · 2024Review
- PRKAG2 syndrome, a rare hypertrophic cardiomyopathy: a Brazilian long-term follow-up with extracardiac disorders.Einstein (Sao Paulo, Brazil) · 2024Article
- Refeeding-associated AMPKNature aging · 2023Article
- Intrafamilial Phenotypical Variability Linked to PRKAG2 Mutation-Family Case Report and Review of the Literature.Life (Basel, Switzerland) · 2022Review
- Animal Models of Dysregulated Cardiac Metabolism.Circulation research · 2022Review
- AKT-mTOR signaling-mediated rescue ofCardiovascular diagnosis and therapy · 2022Article
- Adiponectin receptor agonist ameliorates cardiac lipotoxicity via enhancing ceramide metabolism in type 2 diabetic mice.Cell death & disease · 2022Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
rationaleAMP-activated protein kinase is a master regulator of cell metabolism and an attractive drug target for cancer and metabolic and cardiovascular diseases. Point mutations in the regulatory γ2-subunit of AMP-activated protein kinase (encoded by Prkag2 gene) caused a unique form of human cardiomyopathy characterized by cardiac hypertrophy, ventricular preexcitation, and glycogen storage. Understanding the disease mechanisms of Prkag2 cardiomyopathy is not only beneficial for the patients but also critical to the use of AMP-activated protein kinase as a drug target.
objectiveWe sought to identify the pro-growth-signaling pathway(s) triggered by Prkag2 mutation and to distinguish it from the secondary response to glycogen storage. METHODS AND
resultsIn a mouse model of N488I mutation of the Prkag2 gene (R2M), we rescued the glycogen storage phenotype by genetic inhibition of glucose-6-phosphate-stimulated glycogen synthase activity. Ablation of glycogen storage eliminated the ventricular preexcitation but did not affect the excessive cardiac growth in R2M mice. The progrowth effect in R2M hearts was mediated via increased insulin sensitivity and hyperactivity of Akt, resulting in activation of mammalian target of rapamycin and inactivation of forkhead box O transcription factor-signaling pathways. Consequently, cardiac myocyte proliferation during the postnatal period was enhanced in R2M hearts followed by hypertrophic growth in adult hearts. Inhibition of mammalian target of rapamycin activity by rapamycin or restoration of forkhead box O transcription factor activity by overexpressing forkhead box O transcription factor 1 rescued the abnormal cardiac growth.
conclusionsOur study reveals a novel mechanism for Prkag2 cardiomyopathy, independent of glycogen storage. The role of γ2-AMP-activated protein kinase in cell growth also has broad implications in cardiac development, growth, and regeneration.
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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.