ArticleNature2013
Diabetic hyperglycaemia activates CaMKII and arrhythmias by O-linked glycosylation.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 360 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
360 citing papers in PubMed, 1 synthesis or guideline pooled it, 591 citations in OpenAlex.
- Prognostic value of HbA1c for in-hospital and short-term mortality in patients with acute coronary syndrome: a systematic review and meta-analysis.Cardiovascular diabetology · 2019Pooled it
- Use of an insulin titration protocol based on continuous glucose monitoring in postoperative cardiac surgery patients with type 2 diabetes and prediabetes: a randomized controlled trial.Cardiovascular diabetology · 2025Trial
- Glycemic Control, Cardiac Autoimmunity, and Long-Term Risk of Cardiovascular Disease in Type 1 Diabetes Mellitus.Circulation · 2019Trial
- Timing and duration of diabetes and incident dementia in older adults: a prospective cohort study.Alzheimer's research & therapy · 2026Article
- PFKFB2 Gates a Relationship Between Cardiac Glycolytic Regulation and Electrophysiological Function.Circulation. Arrhythmia and electrophysiology · 2026Article
- Myocardial Ischemia-Reperfusion Injury: Molecular Mechanisms and Innovative Therapeutic Strategies.Reviews in cardiovascular medicine · 2026Review
- Brain O-GlcNAcylation in Neurodegenerative Diseases: Context-Dependent Mechanisms and Precision Therapeutic Translation.Brain sciences · 2026Review
- Exploring the role of CaMKII in exercise-induced cardioprotection.Human cell · 2026Review
- Hyperglycaemia-induced reactive oxygen species production in cardiac ventricular myocytes differs among mammals.The Journal of physiology · 2026Article
- Orchestrating glucose metabolism: PFKFB2 as a signal-integrating conductor in homeostasis and disease.The Journal of biological chemistry · 2026Review
- Maternal hyperglycemia-induced O-GlcNAcylation of CaMKIIδ promotes mtDNA release and cardiac remodeling in offspring.Nature communications · 2026Article
- Cardiac remodelling in type 2 diabetes: Pathophysiological mechanisms and opportunities for multiscale computational modelling and simulation.The Journal of physiology · 2026Review
- PerturbingCells · 2026Article
- Systematic Quantification of Protein O-GlcNAcylation Reveals Common and Cell-Type-Specific Responses to N-Glycosylation Inhibition in Human Cells.Analytical chemistry · 2026Article
- O-GlcNAcylation: A bridge for regulating the function of the "heart-kidney-bone axis".Biochemistry and biophysics reports · 2026Review
- Sodium-Glucose Cotransporter 2 Inhibitors Shorten Echocardiography-Derived Total Atrial Conduction Time in Patients With Type 2 Diabetes Mellitus: A Prospective Pilot Study.Reviews in cardiovascular medicine · 2026Article
- Allosteric activation of RNF20/RNF40-RAD6A-mediated H2BK120 monoubiquitylation by H2BS112 GlcNAcylation.Nature chemical biology · 2026Article
- Peripheral amylin modulation rebalances brain glycolysis and Tau-Ser214 phosphorylation via cAMP-PKA signaling.iScience · 2026Article
- The role of stress hyperglycemia in in-hospital new-onset atrial fibrillation among patients with acute myocardial infarction: a narrative review.Frontiers in cardiovascular medicine · 2026Review
- O-GlcNAcylation in diabetic cardiac remodeling and a proposed endothelial-macrophage-fibroblast network.Frontiers in immunology · 2026Review
300 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is an enzyme with important regulatory functions in the heart and brain, and its chronic activation can be pathological. CaMKII activation is seen in heart failure, and can directly induce pathological changes in ion channels, Ca(2+) handling and gene transcription. Here, in human, rat and mouse, we identify a novel mechanism linking CaMKII and hyperglycaemic signalling in diabetes mellitus, which is a key risk factor for heart and neurodegenerative diseases. Acute hyperglycaemia causes covalent modification of CaMKII by O-linked N-acetylglucosamine (O-GlcNAc). O-GlcNAc modification of CaMKII at Ser 279 activates CaMKII autonomously, creating molecular memory even after Ca(2+) concentration declines. O-GlcNAc-modified CaMKII is increased in the heart and brain of diabetic humans and rats. In cardiomyocytes, increased glucose concentration significantly enhances CaMKII-dependent activation of spontaneous sarcoplasmic reticulum Ca(2+) release events that can contribute to cardiac mechanical dysfunction and arrhythmias. These effects were prevented by pharmacological inhibition of O-GlcNAc signalling or genetic ablation of CaMKIIδ. In intact perfused hearts, arrhythmias were aggravated by increased glucose concentration through O-GlcNAc- and CaMKII-dependent pathways. In diabetic animals, acute blockade of O-GlcNAc inhibited arrhythmogenesis. Thus, O-GlcNAc modification of CaMKII is a novel signalling event in pathways that may contribute critically to cardiac and neuronal pathophysiology in diabetes and other diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.