ArticleMolecular endocrinology (Baltimore, Md.)2012
Insulin-induced endothelial cell cortical actin filament remodeling: a requirement for trans-endothelial insulin transport.
Article in Molecular endocrinology (Baltimore, Md.), 2012. 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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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- Insulin resistance in the 21st century: new takes on an old problem-2025 Diabetes, Diabetes Care, and Diabetologia Expert Forum.Diabetologia · 2026Review
- A microscopic investigation on insulin uptake in human hepatocellular carcinoma-derived HepG2 cells.RSC advances · 2025Article
- Unraveling Skeletal Muscle Insulin Resistance: Molecular Mechanisms and the Restorative Role of Exercise.Circulation research · 2025Review
- Silk Protein Gene Engineering and Its Applications: Recent Advances in Biomedicine Driven by Molecular Biotechnology.Drug design, development and therapy · 2025Review
- Article
- Type I interferon activation and endothelial dysfunction in caveolin-1 insufficiency-associated pulmonary arterial hypertension.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Endothelial insulin receptors differentially control insulin signaling kinetics in peripheral tissues and brain of mice.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Increased muscle blood supply and transendothelial nutrient and insulin transport induced by food intake and exercise: effect of obesity and ageing.The Journal of physiology · 2016Review
- Caveolin-1 phosphorylation regulates vascular endothelial insulin uptake and is impaired by insulin resistance in rats.Diabetologia · 2015Article
- A role for human brain pericytes in neuroinflammation.Journal of neuroinflammation · 2014Article
- Interaction of membrane/lipid rafts with the cytoskeleton: impact on signaling and function: membrane/lipid rafts, mediators of cytoskeletal arrangement and cell signaling.Biochimica et biophysica acta · 2014Review
- The vascular endothelium, a benign restrictive barrier? NO! Role of nitric oxide in regulating insulin action.Diabetes · 2013Article
- Article
- Microvascular dysfunction: an emerging pathway in the pathogenesis of obesity-related insulin resistance.Reviews in endocrine & metabolic disorders · 2013Review
- The endothelial cell: an "early responder" in the development of insulin resistance.Reviews in endocrine & metabolic disorders · 2013Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Insulin's trans-endothelial transport (TET) is critical for its metabolic action on muscle and involves trafficking of insulin bound to its receptor (or at high insulin concentrations, the IGF-I receptor) via caveolae. However, whether caveolae-mediated insulin TET involves actin cytoskeleton organization is unknown. Here we address whether insulin regulates actin filament organization in bovine aortic endothelial cells (bAEC) and whether this affects insulin uptake and TET. We found that insulin induced extensive cortical actin filament remodeling within 5 min. This remodeling was inhibited not only by disruption of actin microfilament organization but also by inhibition of phosphatidylinositol 3-kinase (PI3K) or by disruption of lipid rafts using respective specific inhibitors. Knockdown of either caveolin-1 or Akt using specific small interfering RNA also eliminated the insulin-induced cortical actin filament remodeling. Blocking either actin microfilament organization or PI3K pathway signaling inhibited both insulin uptake and TET. Disruption of actin microfilament organization also reduced the caveolin-1, insulin receptor, and IGF-I receptor located at the plasma membrane. Exposing bAEC for 6 h to either TNFα or IL-6 blocked insulin-induced cortical actin remodeling. Extended exposure (24 h) also inhibited actin expression at both mRNA and protein levels. We conclude that insulin-induced cortical actin filament remodeling in bAEC is required for insulin's TET in a PI3K/Akt and plasma membrane lipid rafts/caveolae-dependent fashion, and proinflammatory cytokines TNFα and IL-6 block this process.
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