ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2015
Hyperketonemia (acetoacetate) upregulates NADPH oxidase 4 and elevates oxidative stress, ICAM-1, and monocyte adhesivity in endothelial cells.
Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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
45 citing papers in PubMed, 66 citations in OpenAlex.
- Effect of statins and ACE inhibitors on the metabolome in the Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT) cohort.Scientific reports · 2026Article
- A blood-based metabolomics study of cardiovascular diseases in Swedish twins reveals apolipoprotein B biology as important for myocardial infarction.GeroScience · 2026Article
- Review
- Glucagon in Pediatric Metabolic Disorders: Pathophysiology and Therapeutic Perspectives.Pediatric reports · 2025Review
- Macrophage energy metabolism in cardiometabolic disease.Molecular and cellular biochemistry · 2025Review
- Association of ultra-processed food-related metabolites with selected biochemical markers in the UK Biobank.Nutrition journal · 2025Article
- Review
- Underlying mechanisms of ketotherapy in heart failure: current evidence for clinical implementations.Frontiers in pharmacology · 2024Review
- Ketone Bodies in Diabetes Mellitus: Friend or Foe?Nutrients · 2023Review
- Plasma metabolomics of oral squamous cell carcinomas based on NMR and MS approaches provides biomarker identification and survival prediction.Scientific reports · 2023Article
- The Role of a Ketogenic Diet in the Treatment of Dementia in Type 2 Diabetes Mellitus.Nutrients · 2023Review
- Gas Chromatography-Mass Spectrometry (GC-MS) Metabolites Analysis in Endometriosis Patients: A Prospective Observational Translational Study.Journal of clinical medicine · 2023Article
- Evaluation of Trace Elements Levels and Construction of Auxiliary Prediction Model in Patients with Diabetes Ketoacidosis in Type 1 Diabetes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- The proteomic effects of ketone bodies: implications for proteostasis and brain proteinopathies.Frontiers in molecular neuroscience · 2023Review
- Regulation of adult stem cell function by ketone bodies.Frontiers in cell and developmental biology · 2023Review
- Molecular Mechanisms for Ketone Body Metabolism, Signaling Functions, and Therapeutic Potential in Cancer.Nutrients · 2022Review
- Article
- The Paradoxical Role of Circulating Ketone Bodies in Glycemic Control of Individuals with Type 2 Diabetes: High Risk, High Reward?Biomolecules · 2022Article
- Ketone Bodies and SIRT1, Synergic Epigenetic Regulators for Metabolic Health: A Narrative Review.Nutrients · 2022Review
- Urine ketone bodies and adverse outcomes in patients with acute ischemic stroke or TIA.Atherosclerosis plus · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND/
aimsThe incidence of developing microvascular dysfunction is significantly higher in type 1 diabetic (T1D) patients. Hyperketonemia (acetoacetate, β-hydroxybutyrate) is frequently found along with hyperglycemia in T1D. Whether hyperketonemia per se contributes to the excess oxidative stress and cellular injury observed in T1D is not known.
methodsHUVEC were treated with ketones in the presence or absence of high glucose for 24 h. NOX4 siRNA was used to specifically knockdown NOX4 expression in HUVEC.
resultsKetones alone or in combination with high glucose treatment cause a significant increase in oxidative stress, ICAM-1, and monocyte adhesivity to HUVEC. Using an antisense approach, we show that ketone induced increases in ROS, ICAM-1 expression, and monocyte adhesion in endothelial cells were prevented in NOX4 knockdown cells.
conclusionThis study reports that elevated levels of ketones upregulate NOX, contributing to increased oxidative stress, ICAM-1 levels, and cellular dysfunction. This provides a novel biochemical mechanism that elucidates the role of hyperketonemia in the excess cellular injury in T1D. New drugs targeting inhibition of NOX seems promising in preventing higher risk of complications associated with T1D.
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.