ArticleMolecular endocrinology (Baltimore, Md.)2009
Insulin acts through FOXO3a to activate transcription of plasminogen activator inhibitor type 1.
Article in Molecular endocrinology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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
15 citing papers in PubMed, 25 citations in OpenAlex.
- The interplay between thrombosis, stress, and social risk factors in trans persons on gender affirming hormone therapy.Research and practice in thrombosis and haemostasis · 2026Article
- Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females.International journal of molecular sciences · 2023Article
- Mechanism of histone deacetylase HDAC2 in FOXO3-mediated trophoblast pyroptosis in preeclampsia.Functional & integrative genomics · 2023Article
- Micro ribonucleic acid-363 regulates the phosphatidylinositol 3-kinase/threonine protein kinase axis by targeting NOTCH1 and forkhead box C2, leading to hepatic glucose and lipids metabolism disorder in type 2 diabetes mellitus.Journal of diabetes investigation · 2022Article
- Epigenetic clock analysis and increased plasminogen activator inhibitor-1 in high-functioning autism spectrum disorder.PloS one · 2022Article
- Delayed maturation of P2 flash visual evoked potential (VEP) latency in newborns of gestational diabetic mothers.Early human development · 2021Article
- Effect of Insulin-Regulated FOXC2 Expression in Adipocyte Differentiation and Insulin Resistance.Diabetes, metabolic syndrome and obesity : targets and therapy · 2020Article
- Autism spectrum disorders: let's talk about glucose?Translational psychiatry · 2019Review
- The Vasculature in Prediabetes.Circulation research · 2018Review
- High glucose and insulin enhance uPA expression, ROS formation and invasiveness in breast cancer-derived cells.Cellular oncology (Dordrecht, Netherlands) · 2016Article
- t-Darpp overexpression in HER2-positive breast cancer confers a survival advantage in lapatinib.Oncotarget · 2015Article
- The PAX3-FOXO1 fusion protein present in rhabdomyosarcoma interferes with normal FOXO activity and the TGF-β pathway.PloS one · 2015Article
- Statins Increase Plasminogen Activator Inhibitor Type 1 Gene Transcription through a Pregnane X Receptor Regulated Element.PloS one · 2015Article
- Clinical mesenchymal stromal cell products undergo functional changes in response to freezing.Cytotherapy · 2015Article
- Forkhead box A1 (FOXA1) is a key mediator of insulin-like growth factor I (IGF-I) activity.Journal of cellular biochemistry · 2012Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Plasminogen activator inhibitor-1 (PAI-1) is an important regulator of fibrinolysis. PAI-1 levels are elevated in type 2 diabetes, and this elevation correlates with macro- and microvascular complications of diabetes. However, the mechanistic link between insulin and up-regulation of PAI-1 is unclear. Here we demonstrate that overexpression of Forkhead-related transcription factor (Fox)O1, FoxO3a, and FoxC1 augment insulin's ability to activate the PAI-1 promoter. In addition, insulin treatment promotes the phosphorylation of nuclear and cytoplasmic Fox03a and an increase of cytoplasmic Fox03a. In contrast, insulin treatment led to the accumulation of phospho-Fox01 only in the cytoplasm. Furthermore, insulin also increased the ability of chimeric LexA-FoxO1, LexA-FoxO3a, and LexA-FoxC1 proteins to increase the activity of a LexA reporter, suggesting that the effect of insulin on FoxO3a was direct. Using small interfering RNA to specifically deplete each of the Fox transcription factors tested, we demonstrate that only reduction of FoxO3a inhibits insulin-increased PAI-1-Luc expression and PAI-1 mRNA accumulation. Finally, chromatin immunoprecipitation assays confirm the presence of FoxO3a on the PAI-1 promoter. These results suggest that FoxO3a mediates insulin-increased PAI-1 gene expression.
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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.