ArticleMicrocirculation (New York, N.Y. : 1994)2018
Insulin resistance disrupts cell integrity, mitochondrial function, and inflammatory signaling in lymphatic endothelium.
Article in Microcirculation (New York, N.Y. : 1994), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Dysfunctional adipose tissue-lymphatic crosstalk in obesity.Nature reviews. Endocrinology · 2026Review
- Vaginal aging: from concealed symptoms to defined biomarkers.npj aging · 2026Review
- Exercise training ameliorates myocardial dysfunction through fibronectin-mediated mechanotransduction in a swine model of ischemic heart disease.American journal of physiology. Heart and circulatory physiology · 2026Article
- Pain and lymphedema characteristics of women with breast cancer-related lymphedema with and without type 2 diabetes mellitus.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Article
- Obesity-Associated Conditions Hinder Solute Drainage Function of Engineered Human Lymphatic Vessels.Cellular and molecular bioengineering · 2025Article
- Lymphedema pathogenesis involves antigen-driven expansion of CD4+ T cells in skin.Frontiers in immunology · 2025Article
- Article
- Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce the risk of developing cancer-related lymphedema following axillary lymph node dissection (ALND).Frontiers in pharmacology · 2024Article
- Neuroprotective effects of GLP-1 class drugs in Parkinson's disease.Frontiers in neurology · 2024Review
- Article
- Promoting Lymphangiogenesis and Lymphatic Growth and Remodeling to Treat Cardiovascular and Metabolic Diseases.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
- Lymphatic Collecting Vessel: New Perspectives on Mechanisms of Contractile Regulation and Potential Lymphatic Contractile Pathways to Target in Obesity and Metabolic Diseases.Frontiers in pharmacology · 2022Review
- Diabetes and Its Cardiovascular Complications: Comprehensive Network and Systematic Analyses.Frontiers in cardiovascular medicine · 2022Review
- Article
- Increased expression of fragmented tRNA promoted neuronal necrosis.Cell death & disease · 2021Article
- Epsins in vascular development, function and disease.Cellular and molecular life sciences : CMLS · 2021Review
- CXCL11-CXCR3 Axis Mediates Tumor Lymphatic Cross Talk and Inflammation-Induced Tumor, Promoting Pathways in Head and Neck Cancers.The American journal of pathology · 2020Article
- Neurodegenerative Diseases - Is Metabolic Deficiency the Root Cause?Frontiers in neuroscience · 2020Review
- The Role of Lymphatic Vascular Function in Metabolic Disorders.Frontiers in physiology · 2020Review
- Regulation of Lymphatic Function in Obesity.Frontiers in physiology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectiveLymphatic vessel dysfunction and increased lymph leakage have been directly associated with several metabolic diseases. However, the underlying cellular mechanisms causing lymphatic dysfunction have not been determined. Aberrant insulin signaling affects the metabolic function of cells and consequently impairs tissue function. We hypothesized that insulin resistance in LECs decreases eNOS activity, disrupts barrier integrity increases permeability, and activates mitochondrial dysfunction and pro-inflammatory signaling pathways.
methodsLECs were treated with insulin and/or glucose to determine the mechanisms leading to insulin resistance.
resultsAcute insulin treatment increased eNOS phosphorylation and NO production in LECs via activation of the PI3K/Akt signaling pathway. Prolonged hyperglycemia and hyperinsulinemia induced insulin resistance in LECs. Insulin-resistant LECs produced less NO due to a decrease in eNOS phosphorylation and showed a significant decrease in impedance across an LEC monolayer that was associated with disruption in the adherence junctional proteins. Additionally, insulin resistance in LECs impaired mitochondrial function by decreasing basal-, maximal-, and ATP-linked OCRs and activated NF-κB nuclear translocation coupled with increased pro-inflammatory signaling.
conclusionOur data provide the first evidence that insulin resistance disrupts endothelial barrier integrity, decreases eNOS phosphorylation and mitochondrial function, and activates inflammation in LECs.
Indexed as
Identifiers
What OpenQuestion holds
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.