ArticleDiabetes2015
Metformin treatment in the period after stroke prevents nitrative stress and restores angiogenic signaling in the brain in diabetes.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 71 citations in OpenAlex.
- Effects of Prior Metformin Use on Stroke Outcomes in Diabetes Patients with Acute Ischemic Stroke Receiving Endovascular Treatment.Biomedicines · 2024Article
- Deferoxamine prevents poststroke memory impairment in female diabetic rats: potential links to hemorrhagic transformation and ferroptosis.American journal of physiology. Heart and circulatory physiology · 2023Article
- Vascular contributions to cognitive impairment/dementia in diabetes: role of endothelial cells and pericytes.American journal of physiology. Cell physiology · 2022Review
- GLP-1 receptor nitration contributes to loss of brain pericyte function in a mouse model of diabetes.Diabetologia · 2022Article
- Impact of diabetes and ischemic stroke on the cerebrovasculature: A female perspective.Neurobiology of disease · 2022Review
- Hyperglycemia-triggered ATF6-CHOP pathway aggravates acute inflammatory liver injury by β-catenin signaling.Cell death discovery · 2022Article
- Metformin use is associated with low risk of case fatality and disability rates in first-ever stroke patients with type 2 diabetes.Therapeutic advances in chronic disease · 2022Article
- Deferoxamine Treatment Prevents Post-Stroke Vasoregression and Neurovascular Unit Remodeling Leading to Improved Functional Outcomes in Type 2 Male Diabetic Rats: Role of Endothelial Ferroptosis.Translational stroke research · 2021Article
- Phosphorylation of Akt at Thr308 regulates p-eNOS Ser1177 during physiological conditions.FEBS open bio · 2021Article
- Three-dimensional remodeling of functional cerebrovascular architecture and gliovascular unit in leptin receptor-deficient mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Repurposing metformin to treat age-related neurodegenerative disorders and ischemic stroke.Life sciences · 2021Review
- Treatment with an Angiopoietin-1 mimetic peptide promotes neurological recovery after stroke in diabetic rats.CNS neuroscience & therapeutics · 2021Article
- Novel Targets and Interventions for Cognitive Complications of Diabetes.Frontiers in physiology · 2021Review
- Metformin coordinates osteoblast/osteoclast differentiation associated with ischemic osteonecrosis.Aging · 2020Article
- Diabetes aggravates renal ischemia and reperfusion injury in rats by exacerbating oxidative stress, inflammation, and apoptosis.Renal failure · 2019Article
- MMP10 Promotes Efficient Thrombolysis After Ischemic Stroke in Mice with Induced Diabetes.Translational stroke research · 2019Article
- NLRP3 inflammasome inhibition with MCC950 improves diabetes-mediated cognitive impairment and vasoneuronal remodeling after ischemia.Pharmacological research · 2019Article
- Inhibition of Toll-Like Receptor-4 (TLR-4) Improves Neurobehavioral Outcomes After Acute Ischemic Stroke in Diabetic Rats: Possible Role of Vascular Endothelial TLR-4.Molecular neurobiology · 2019Article
- Post-stroke neovascularization and functional outcomes differ in diabetes depending on severity of injury and sex: Potential link to hemorrhagic transformation.Experimental neurology · 2019Article
- Inhibition of Ephrin-B2 in brain pericytes decreases cerebral pathological neovascularization in diabetic rats.PloS one · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Diabetes impedes vascular repair and causes vasoregression in the brain after stroke, but mechanisms underlying this response are still unclear. We hypothesized that excess peroxynitrite formation in diabetic ischemia/reperfusion (I/R) injury inactivates the p85 subunit of phosphoinositide 3-kinase (PI3K) by nitration and diverts the PI3K-Akt survival signal to the p38-mitogen-activated protein kinase apoptosis pathway. Nitrotyrosine (NY), Akt and p38 activity, p85 nitration, and caspase-3 cleavage were measured in brains from control, diabetic (GK), or metformin-treated GK rats subjected to sham or stroke surgery and in brain microvascular endothelial cells (BMVECs) from Wistar and GK rats subjected to hypoxia/reoxygenation injury. GK rat brains showed increased NY, caspase-3 cleavage, and p38 activation and decreased Akt activation. Metformin attenuated stroke-induced nitrative signaling in GK rats. GK rat BMVECs showed increased basal nitrative stress compared with controls. A second hit by hypoxia/reoxygenation injury dramatically increased the nitration of p85 and activation of p38 but decreased Akt. These effects were associated with impairment of angiogenic response and were restored by treatment with the peroxynitrite scavenger 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron III chloride or the nitration inhibitor epicatechin. Our results provide evidence that I/R-induced peroxynitrite inhibits survival, induces apoptosis, and promotes peroxynitrite as a novel therapeutic target for the improvement of reparative angiogenesis after stroke 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.