ArticleThe Journal of clinical investigation2018
Insulin exits skeletal muscle capillaries by fluid-phase transport.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Microvascular insulin resistance with enhanced muscle glucose disposal in CD36 deficiency.Diabetologia · 2025Trial
- Palmitoylation calibrates mitochondrial transport of insulin across the endothelium in insulin resistance.bioRxiv : the preprint server for biology · 2026Article
- Synthesis and Characterisation of Bioactive Fluorescent FITC-Insulin Glulisine Conjugates for Potential Use in Insulin Delivery.Pharmaceutics · 2026Article
- Unraveling Skeletal Muscle Insulin Resistance: Molecular Mechanisms and the Restorative Role of Exercise.Circulation research · 2025Review
- Metabolic and vascular insulin resistance: partners in the pathogenesis of cardiovascular disease in diabetes.American journal of physiology. Heart and circulatory physiology · 2025Review
- Increased cGMP improves microvascular exercise training adaptations in diet-induced obesity.American journal of physiology. Endocrinology and metabolism · 2025Article
- Endothelial β1-integrins are necessary for microvascular function and glucose uptake.American journal of physiology. Endocrinology and metabolism · 2024Article
- Endothelial β1 Integrins are Necessary for Microvascular Function and Glucose Uptake.bioRxiv : the preprint server for biology · 2024Article
- Article
- Cerebrovascular insulin receptors are defective in Alzheimer's disease.Brain : a journal of neurology · 2023Article
- Targeting the vasculature in cardiometabolic disease.The Journal of clinical investigation · 2022Review
- Synthesis and Identification of Biologically Active Mono-Labelled FITC-Insulin Conjugate.Journal of fluorescence · 2022Article
- Glucose Uptake by Skeletal Muscle within the Contexts of Type 2 Diabetes and Exercise: An Integrated Approach.Nutrients · 2022Review
- Imaging in experimental models of diabetes.Acta diabetologica · 2022Review
- Capillary Endothelial Insulin Transport: The Rate-limiting Step for Insulin-stimulated Glucose Uptake.Endocrinology · 2022Review
- Skeletal Muscle Microvascular Dysfunction in Obesity-Related Insulin Resistance: Pathophysiological Mechanisms and Therapeutic Perspectives.International journal of molecular sciences · 2022Review
- Insulin Clearance in Obesity and Type 2 Diabetes.International journal of molecular sciences · 2022Review
- Luseogliflozin, a SGLT2 Inhibitor, Does Not Affect Glucose Uptake Kinetics in Renal Proximal Tubules of Live Mice.International journal of molecular sciences · 2021Article
- The Insulin Receptor Mediates Insulin's Early Plasma Clearance by Liver, Muscle, and Kidney.Biomedicines · 2021Article
- Effects of imatinib on vascular insulin sensitivity and free fatty acid transport in early weight gain.PloS one · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Before insulin can stimulate myocytes to take up glucose, it must first move from the circulation to the interstitial space. The continuous endothelium of skeletal muscle (SkM) capillaries restricts insulin's access to myocytes. The mechanism by which insulin crosses this continuous endothelium is critical to understand insulin action and insulin resistance; however, methodological obstacles have limited understanding of endothelial insulin transport in vivo. Here, we present an intravital microscopy technique to measure the rate of insulin efflux across the endothelium of SkM capillaries. This method involves development of a fully bioactive, fluorescent insulin probe, a gastrocnemius preparation for intravital microscopy, an automated vascular segmentation algorithm, and the use of mathematical models to estimate endothelial transport parameters. We combined direct visualization of insulin efflux from SkM capillaries with modeling of insulin efflux kinetics to identify fluid-phase transport as the major mode of transendothelial insulin efflux in mice. Model-independent experiments demonstrating that insulin movement is neither saturable nor affected by insulin receptor antagonism supported this result. Our finding that insulin enters the SkM interstitium by fluid-phase transport may have implications in the pathophysiology of SkM insulin resistance as well as in the treatment of diabetes with various insulin analogs.
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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.