ArticleCirculation research2014
Activation of AKT by O-linked N-acetylglucosamine induces vascular calcification in diabetes mellitus.
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 104 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
104 citing papers in PubMed, 1 synthesis or guideline pooled it, 163 citations in OpenAlex.
- Cross-ancestry analyses of Chinese and European populations reveal insights into the genetic architecture and disease implication of metabolites.Cell genomics · 2025Pooled it
- Amphilimus- vs. zotarolimus-eluting stents in patients with diabetes mellitus and coronary artery disease: the SUGAR trial.European heart journal · 2022Trial
- Vascular calcification: pathogenic mechanisms, signaling crosstalk and translational therapeutics.Signal transduction and targeted therapy · 2026Review
- Hexosamine Biosynthetic Pathway and Fatty Acid β-Oxidative Imbalance: A Key Mechanism by Which Abnormal Macrophage Lipophagy Promotes Atherosclerosis in Diabetes.Cardiovascular drugs and therapy · 2026Review
- Semaglutide Alleviates LPS-Induced Cognitive Disorder via O-GlcNAcylation of AKT-mTOR Signaling Pathway Components.Neuromolecular medicine · 2026Article
- Phosphoproteomics in Vascular Biology and Disease: Illuminating Signaling in the Vessel.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- O-GlcNAcylation: the metabolic-immune translator in tumor evolution and treatment.Molecular medicine (Cambridge, Mass.) · 2026Review
- Systematic Quantification of Protein O-GlcNAcylation Reveals Common and Cell-Type-Specific Responses to N-Glycosylation Inhibition in Human Cells.Analytical chemistry · 2026Article
- Dammarenediol II enhances etoposide-induced apoptosis by targeting O-GlcNAc transferase and Akt/GSK3β/mTOR signaling in liver cancer.Molecular oncology · 2026Article
- Peripheral Vascular Calcification.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Review
- Vascular Smooth Muscle Cell-Specific BCAT2 Deficiency Attenuates Diabetic Atherosclerotic Calcification via Histone Propionylation.Research (Washington, D.C.) · 2026Article
- Reprogrammed glucose metabolism in vascular smooth muscle cells and its implications for vascular diseases.Pharmacological research · 2025Review
- O-GlcNAcase Inhibitor Improves Denervation-Induced Muscle Atrophy in Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
- Exploring the metabolic signaling network of GFPT in cancer.Cell death discovery · 2025Review
- Glyoxalase-1 overexpression attenuates arterial wall stiffening in diabetic mice.Cardiovascular diabetology · 2025Article
- TET2 suppresses vascular calcification by forming an inhibitory complex with HDAC1/2 and SNIP1 independent of demethylation.The Journal of clinical investigation · 2025Article
- O-GlcNAcylation of glutaminase isoform KGA inhibits ferroptosis through activation of glutaminolysis in hepatoblastoma.Cell death discovery · 2025Article
- Mib2 Regulates Lipid Metabolism in Heart Failure With Preserved Ejection Fraction via the Runx2-Hmgcs2 Axis.Journal of cellular and molecular medicine · 2025Article
- Metabolic and Mitochondrial Dysregulations in Diabetic Cardiac Complications.International journal of molecular sciences · 2025Review
44 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
rationaleVascular calcification is a serious cardiovascular complication that contributes to the increased morbidity and mortality of patients with diabetes mellitus. Hyperglycemia, a hallmark of diabetes mellitus, is associated with increased vascular calcification and increased modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation).
objectiveWe sought to determine the role of protein O-GlcNAcylation in regulating vascular calcification and the underlying mechanisms. METHODS AND
resultsLow-dose streptozotocin-induced diabetic mice exhibited increased aortic O-GlcNAcylation and vascular calcification, which was also associated with impaired aortic compliance in mice. Elevation of O-GlcNAcylation by administration of Thiamet-G, a potent inhibitor for O-GlcNAcase that removes O-GlcNAcylation, further accelerated vascular calcification and worsened aortic compliance of diabetic mice in vivo. Increased O-GlcNAcylation, either by Thiamet-G or O-GlcNAcase knockdown, promoted calcification of primary mouse vascular smooth muscle cells. Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell upregulated expression of the osteogenic transcription factor Runx2 and enhanced activation of AKT. O-GlcNAcylation of AKT at two new sites, T430 and T479, promoted AKT phosphorylation, which in turn enhanced vascular smooth muscle cell calcification. Site-directed mutation of AKT at T430 and T479 decreased O-GlcNAcylation, inhibited phosphorylation of AKT at S473 and binding of mammalian target of rapamycin complex 2 to AKT, and subsequently blocked Runx2 transactivity and vascular smooth muscle cell calcification.
conclusionsO-GlcNAcylation of AKT at 2 new sites enhanced AKT phosphorylation and activation, thus promoting vascular calcification. Our studies have identified a novel causative effect of O-GlcNAcylation in regulating vascular calcification in diabetes mellitus and uncovered a key molecular mechanism underlying O-GlcNAcylation-mediated activation of AKT.
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.