ArticleFrontiers in pharmacology2018
Metformin Modulates High Glucose-Incubated Human Umbilical Vein Endothelial Cells Proliferation and Apoptosis Through AMPK/CREB/BDNF Pathway.
Article in Frontiers in pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
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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.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Effects of acarbose and metformin on the inflammatory state in newly diagnosed type 2 diabetes patients: a one-year randomized clinical study.Drug design, development and therapy · 2019Trial
- Brown Yar Ko Rice Protects Against Hyperglycemia-Induced Endothelial Injury via Antioxidant and SIRT1 Activation.Scientifica · 2026Article
- Novel Insights into the Mechanism and Treatment of Diabetes-Related Brain Complications: Focusing on the Blood-Brain Barrier Impairment.Aging and disease · 2025Review
- Anti-Inflammatory Potential of the Anti-Diabetic Drug Metformin in the Prevention of Inflammatory Complications and Infectious Diseases Including COVID-19: A Narrative Review.International journal of molecular sciences · 2024Review
- Profiling of Differentially Expressed MicroRNAs in Human Umbilical Vein Endothelial Cells Exposed to Hyperglycemia via RNA Sequencing.Life (Basel, Switzerland) · 2023Article
- Overcoming chemoresistance in non-angiogenic colorectal cancer by metformin via inhibiting endothelial apoptosis and vascular immaturity.Journal of pharmaceutical analysis · 2023Article
- Feto-placental endothelial dysfunction in Gestational Diabetes Mellitus under dietary or insulin therapy.BMC endocrine disorders · 2023Article
- Article
- Acute Administration of Metformin Protects Against Neuronal Apoptosis Induced by Cerebral Ischemia-Reperfusion InjuryFrontiers in pharmacology · 2022Article
- Metformin Reduces Vascular Assembly in High Glucose-Treated Human Microvascular Endothelial Cells in An AMPK-Independent Manner.Cell journal · 2021Article
- Isoquercitrin protects HUVECs against high glucose‑induced apoptosis through regulating p53 proteasomal degradation.International journal of molecular medicine · 2021Article
- Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function.Theranostics · 2021Review
- Article
- Metformin decreases hyaluronan synthesis by vascular smooth muscle cells.Journal of investigative medicine : the official publication of the American Federation for Clinical Research · 2020Article
- Metformin Ameliorates Gestational Diabetes Mellitus-Induced Endothelial DysfunctionFrontiers in pharmacology · 2020Article
- Hydrogen Sulfide Protects Against High Glucose-Induced Human Umbilical Vein Endothelial Cell Injury Through Activating PI3K/Akt/eNOS Pathway.Drug design, development and therapy · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cardiovascular disease (CVD) is a leading cause of mortality and morbidity among patients with diabetes. Endothelial dysfunction is an early physiological event in CVD. Metformin, a common oral antihyperglycemic agent, has been demonstrated to directly affect endothelial cell function. Brain-derived neurotrophic factor (BDNF), originally discovered in the brain as a neurotrophin, has also been reported to play a protective role in the cardiovascular system. In our study, we demonstrated that high glucose (HG) reduced cell proliferation and induced cell apoptosis via changes in BDNF expression and that metformin reversed the effects of HG injury by upregulating BDNF expression. Furthermore, we found that cyclic AMP response element binding (CREB) phosphorylation was reduced in HG-treated human umbilical vein endothelial cells (HUVECs), and this effect was reversed by the metformin treatment. However, the metformin effect on BDNF levels in HG-incubated HUVECs was blocked by a CREB inhibitor, which indicated that BDNF expression is regulated by metformin through CREB activation. In addition, we found that adenosine monophosphate-activated protein kinase (AMPK) activation is involved in CREB/BDNF regulation in HG-incubated HUVECs treated with metformin and that an AMPK inhibitor impaired the protective effects of metformin on HG-treated HUVECs. In conclusion, this study demonstrated that metformin affects cell proliferation and apoptosis via the AMPK/CREB/BDNF pathway in HG-incubated HUVECs.
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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 OpenQuestion graph.