ArticleDiabetes2008
Upregulation of mitochondrial uncoupling protein-2 by the AMP-activated protein kinase in endothelial cells attenuates oxidative stress in diabetes.
Article in Diabetes, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. It is linked to trial NCT02633488 (Effect of Metformin on Insulin Sensitivity and Pan-Arterial Vascular Function in Adults With Metabolic Syndrome), which is not on this map. Cited by 90 papers.
What it found
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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.
Effect of Metformin on Insulin Sensitivity and Pan-Arterial Vascular Function in Adults With Metabolic Syndrome
Who cites it
90 citing papers in PubMed, 164 citations in OpenAlex.
- Article
- Deciphering Uncoupling Proteins in Cellular Homeostasis and Metabolic Health.International journal of biological sciences · 2026Review
- Hypoglycaemic stimulation of macrophage cytokine release is suppressed by AMP-activated protein kinase activation.Diabetic medicine : a journal of the British Diabetic Association · 2025Article
- Celastrol alleviates diabetic vascular injury via Keap1/Nrf2-mediated anti-inflammation.Frontiers in pharmacology · 2024Article
- Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease.Journal of translational medicine · 2023Review
- Expressions of mRNA and encoded proteins of mitochondrial uncoupling protein genes (Archives of endocrinology and metabolism · 2023Article
- The pleiotropic AMPK-CncC signaling pathway regulates the trade-off between detoxification and reproduction.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- In Vitro Modeling of Diabetes Impact on Vascular Endothelium: Are Essentials Engaged to Tune Metabolism?Biomedicines · 2022Review
- Role of curcumin in ameliorating hypertension and associated conditions: a mechanistic insight.Molecular and cellular biochemistry · 2022Review
- Endothelial UCP2 Is a Mechanosensitive Suppressor of Atherosclerosis.Circulation research · 2022Article
- Protective Role of Mitochondrial Uncoupling Proteins against Age-Related Oxidative Stress in Type 2 Diabetes Mellitus.Antioxidants (Basel, Switzerland) · 2022Review
- Mitochondrial contributions to vascular endothelial dysfunction, arterial stiffness, and cardiovascular diseases.American journal of physiology. Heart and circulatory physiology · 2021Review
- Dapagliflozin attenuates hypoxia/reoxygenation-caused cardiac dysfunction and oxidative damage through modulation of AMPK.Cell & bioscience · 2021Article
- Beneficial Effect ofEvidence-based complementary and alternative medicine : eCAM · 2021Article
- Effect of Oxidative Stress on Diaphragm Dysfunction and Exercise Intervention in Chronic Obstructive Pulmonary Disease.Frontiers in physiology · 2021Review
- Article
- α1AMP-Activated Protein Kinase Protects against Lipopolysaccharide-Induced Endothelial Barrier Disruption via Junctional Reinforcement and Activation of the p38 MAPK/HSP27 Pathway.International journal of molecular sciences · 2020Article
- AMPK, Mitochondrial Function, and Cardiovascular Disease.International journal of molecular sciences · 2020Review
- Activation of the AMP-related kinase (AMPK) induces renal vasodilatation and downregulates Nox-derived reactive oxygen species (ROS) generation.Redox biology · 2020Article
- Carnosine Activates Cellular Stress Response in Podocytes and Reduces Glycative and Lipoperoxidative Stress.Biomedicines · 2020Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
- Retraction · 2023-05-15Concerns/Issues about Image · Duplication of/in Image · Investigation by Journal/Publisher · Unreliable Results and/or Conclusions ·
- Retracted
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveRecent evidence suggests that the AMP-activated protein kinase (AMPK) is an important therapeutic target for diabetes. The present study was conducted to determine how AMPK activation suppressed tyrosine nitration of prostacyclin synthase in diabetes. RESEARCH DESIGN AND
methodsConfluent human umbilical vein endothelial cells (HUVECs) or mice were treated with 5-amino-4-imidazole carboxamide riboside (AICAR) for the detection of AMPK phosphorylation and the expression of mitochondrial uncoupling protein (UCP)-2.
resultsExposure of HUVECs to high glucose (30 mmol/l) increased superoxide anions (O(2).(-)) and prostacyclin synthase nitration. In addition, overexpression of constitutively active AMPK (Ad-CA-AMPK) or the addition of AICAR reduced both O(2).(-) and prostacyclin synthase nitration caused by high glucose, whereas adenoviral overexpression of dominant-negative AMPK mutants (Ad-DN-AMPK) enhanced the latter effects of high glucose. Exposure of HUVECs to either AICAR or metformin caused AMPK-dependent upregulation of both UCP-2 mRNA and UCP-2 protein. Furthermore, overexpression of UCP-2 significantly ablated both O(2).(-) and prostacyclin synthase nitration triggered by high glucose. Furthermore, overexpression of Ad-CA-AMPK increased, whereas overexpression of Ad-DN-AMPK inhibited AICAR-induced phosphorylation of p38 kinase at Thr180/Tyr182. Inhibition of p38 kinase with SB239063, which had no effect on AICAR-induced AMPK-Thr172 phosphorylation, dose dependently suppressed AICAR-induced upregulation of UCP-2, suggesting that AMPK lies upstream of p38 kinase. Finally, AICAR markedly increased UCP-2 expression and reduced both O(2).(-) and prostacyclin synthase nitration in diabetic wild-type mice but not in their AMPKalpha2-deficient counterparts in vivo.
conclusionsWe conclude that AMPK activation increases UCP-2, resulting in the inhibition of both O(2).(-) and prostacyclin synthase nitration in diabetes.
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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 Socratic graph.