ArticleJournal of the American Heart Association2017
Cardiac Insulin Signaling Regulates Glycolysis Through Phosphofructokinase 2 Content and Activity.
Article in Journal of the American Heart Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- Orchestrating glucose metabolism: PFKFB2 as a signal-integrating conductor in homeostasis and disease.The Journal of biological chemistry · 2026Review
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Glucose Metabolic Enzyme PFKFB3 in Cardiopulmonary Vascular Health and Disease.Circulation research · 2026Review
- PFKFB2 Is Pivotal for Metabolic Flexibility and Differential Glucose Utilization.Journal of the American Heart Association · 2025Article
- The effect of enhanced glycolysis on cardiac aging.GeroScience · 2025Article
- Cardiomyocyte regeneration after infarction: changes, opportunities and challenges.Molecular and cellular biochemistry · 2025Review
- Article
- RNA-Seq Analysis of Glycolysis Regulation of Avian Leukosis Virus Subgroup J Replication.Animals : an open access journal from MDPI · 2024Article
- Loss of Cardiac PFKFB2 Drives Metabolic, Functional, and Electrophysiological Remodeling in the Heart.Journal of the American Heart Association · 2024Article
- The role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches.Basic research in cardiology · 2023Review
- Increased cardiac PFK-2 protects against high-fat diet-induced cardiomyopathy and mediates beneficial systemic metabolic effects.iScience · 2023Article
- Maternal Undernutrition Induces Cell Signalling and Metabolic Dysfunction in Undifferentiated Mouse Embryonic Stem Cells.Stem cell reviews and reports · 2023Article
- Novel Molecular Networks and Regulatory MicroRNAs in Type 2 Diabetes Mellitus: Multiomics Integration and Interactomics Study.JMIR bioinformatics and biotechnology · 2022Article
- Sod1 integrates oxygen availability to redox regulate NADPH production and the thiol redoxome.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Heart failure in diabetes.Metabolism: clinical and experimental · 2021Review
- Effects of Lipid Overload on Heart in Metabolic Diseases.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2021Review
- PFKFB3-dependent glucose metabolism regulates 3T3-L1 adipocyte development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Plant-DerivedNutrients · 2021Article
- GFAT and PFK genes show contrasting regulation of chitin metabolism in Nilaparvata lugens.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe healthy heart has a dynamic capacity to respond and adapt to changes in nutrient availability. Diabetes mellitus disrupts this metabolic flexibility and promotes cardiomyopathy through mechanisms that are not completely understood. Phosphofructokinase 2 (PFK-2) is a primary regulator of cardiac glycolysis and substrate selection, yet its regulation under normal and pathological conditions is unknown. This study was undertaken to determine how changes in insulin signaling affect PFK-2 content, activity, and cardiac metabolism. METHODS AND
resultsStreptozotocin-induced diabetes mellitus, high-fat diet feeding, and fasted mice were used to identify how decreased insulin signaling affects PFK-2 and cardiac metabolism. Primary adult cardiomyocytes were used to define the mechanisms that regulate PFK-2 degradation. Both type 1 diabetes mellitus and a high-fat diet induced a significant decrease in cardiac PFK-2 protein content without affecting its transcript levels. Overnight fasting also induced a decrease in PFK-2, suggesting it is rapidly degraded in the absence of insulin signaling. An unbiased metabolomic study demonstrated that decreased PFK-2 in fasted animals is accompanied by an increase in glycolytic intermediates upstream of phosphofructokianse-1, whereas those downstream are diminished. Mechanistic studies using cardiomyocytes showed that, in the absence of insulin signaling, PFK-2 is rapidly degraded via both proteasomal- and chaperone-mediated autophagy.
conclusionsThe loss of PFK-2 content as a result of reduced insulin signaling impairs the capacity to dynamically regulate glycolysis and elevates the levels of early glycolytic intermediates. Although this may be beneficial in the fasted state to conserve systemic glucose, it represents a pathological impairment in diabetes mellitus.
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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.