The DOI matches its Crossref record; 97 of the 97 references it cites were found in a registry or an index.
The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action
Open accessAbstract
Evidence suggests that insulin delivery to skeletal muscle interstitium is the rate-limiting step in insulin-stimulated muscle glucose uptake and that this process is impaired by insulin resistance. In this review we examine the basis for the hypothesis that insulin acts on the vasculature at three discrete steps to enhance its own delivery to muscle: (1) relaxation of resistance vessels to increase total blood flow; (2) relaxation of pre-capillary arterioles to increase the microvascular exchange surface perfused within skeletal muscle (microvascular recruitment); and (3) the trans-endothelial transport (TET) of insulin. Insulin can relax resistance vessels and increase blood flow to skeletal muscle. However, there is controversy as to whether this occurs at physiological concentrations of, and exposure times to, insulin. The microvasculature is recruited more quickly and at lower insulin concentrations than are needed to increase total blood flow, a finding consistent with a physiological role for insulin in muscle insulin delivery. Microvascular recruitment is impaired by obesity, diabetes and nitric oxide synthase inhibitors. Insulin TET is a third potential site for regulating insulin delivery. This is underscored by the consistent finding that steady-state insulin concentrations in plasma are approximately twice those in muscle interstitium. Recent in vivo and in vitro findings suggest that insulin traverses the vascular endothelium via a trans-cellular, receptor-mediated pathway, and emerging data indicate that insulin acts on the endothelium to facilitate its own TET. Thus, muscle insulin delivery, which is rate-limiting for its metabolic action, is itself regulated by insulin at multiple steps. These findings highlight the need to further understand the role of the vascular actions of insulin in metabolic regulation.
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“In vitro and rodent studies show that aldosterone-induced mineralocorticoid activation impairs insulin sensitivity in adipocytes and skeletal muscle [40,41].”
From Insulin sensitivity and pancreatic β-cell function in patients with primary aldosteronism (2021) · cites this paper as [41]
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“endothelial dysfunction 48 with consequent blunting of physiological vasodilation.49”
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Citations
Cites
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Cited by
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The Vascular Endothelium and Human Diseases
Rajendran, P., Rengarajan, T., Thangavel, J., Nishigaki, Y., Sakthisekaran, D., Sethi, G., & Nishigaki, I. (2013) · International Journal of Biological Sciences · doi:10.7150/ijbs.7502 · Cited by 1,550
Schalkwijk, C., & Stehouwer, C. D. A. (2019) · Physiological Reviews · doi:10.1152/physrev.00001.2019 · Cited by 649
Landsberg, L., Aronne, L. J., Beilin, L. J., Burke, V., Igel, L. I., Lloyd‐Jones, D., & Sowers, J. (2013) · The Journal of Clinical Hypertension · doi:10.1111/jch.12049 · Cited by 528
Diabetic Microvascular Disease: An Endocrine Society Scientific Statement
Barrett, E. J., Liu, Z., Khamaisi, M., King, G. L., Klein, R., Klein, R., Hughes, T. M., Craft, S., Freedman, B. I., Bowden, D. W., et al. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01922 · Cited by 537
Self-citationThe cell biology of systemic insulin function
Tokarz, V. L., MacDonald, P. E., & Klip, A. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201802095 · Cited by 471
“Insulin action in target tissues is temporally linked to these vascular effects (Barrett et al., 2009); in particular, the full stimulation of skeletal muscle glucose uptake in vivo is contingent on prior NO-mediated vasodilation (Vincent et al., 2003; Bradley et al., 2013).”
BackgroundInfluential
Metadata
- Authors
- Barrett, E. J., Eggleston, E. M., Inyard, A. C., Wang, H., Li, G., Chai, W., & Liu, Z.
- Affiliations
- University of Virginia Health System (US)
- Corresponding author
- Barrett, E. J.
- Venue
- Diabetologia
- Published
- 2009-03-13
- Volume
- 52
- Issue
- 5
- Pages
- 752-764
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC2704146
- OpenAlex
- W2033746638
- Semantic Scholar
- 1734beade6892acf92cbb3b6f1dfe6b7bf05b1ef
- Cited by
- 323
- References
- 97
- Citations by year
- 2026: 12 · 2025: 7 · 2024: 9 · 2023: 9 · 2022: 14 · 2021: 19 · 2020: 13 · 2019: 18 · 2018: 10 · 2017: 19 · 2016: 15 · 2015: 20 · 2014: 19 · 2013: 51 · 2012: 29
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Virginia
- University College London
- Vrije Universiteit Amsterdam
- National Institutes of Health (5p30dk063609-05, RR-00847)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK073759, R01DK073759, DK057878, DK-063609, P30-DK-063609, R01DK057878)
- National Center for Research Resources (RR 00847, M01RR000847)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- insulin, skeletal muscle, insulin delivery, resistance vessels, blood flow, insulin resistance, nitric oxide synthase, obesity, diabetes mellitus, muscle glucose uptake, endothelium
- MeSH terms
- Animals, Glucose, Homeostasis, Humans, Hyperinsulinism, Insulin, Insulin Resistance, Kinetics, Microcirculation, Glucose Clamp Technique, Microdialysis, Muscle, Skeletal
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