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Cited by 323Diabetes, Cardiovascular Risks, and LipoproteinsMetabolism, Diabetes, and CancerDiabetes Management and Research

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

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Barrett, E. J., Eggleston, E. M., Inyard, A. C., Wang, H., Li, G., Chai, W., Liu, Z.·2009·Diabetologia
DOI 10.1007/s00125-009-1313-zPMC PMC2704146
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Abstract

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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  1. Natali A, Galvan AQ, Pecori N, Sanna G, Toschi E, Ferrannini E (1998) vasodilation with sodium nitroprusside does not improve insulin action in essential hypertension. Hypertension 31:632–636 · DOI
  2. Wang H, Wang AX, Barrett EJ (2008) siRNA-mediated silencing of caveolin-1 inhibits insulin transport but enhances insulin-stimulated nitric oxide production. Diabetes 57:A383 (Abstract)
  3. Kubota T, Hubota N, Kozono H et al (2008) Insulin signaling in endothelial cells participates in the regulation of skeletal muscle insulin sensitivity. Diabetes 57:A369 (Abstract)

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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.
ORCID
Venue
Diabetologia
Publisher
Springer Science and Business Media LLC
Published
2009-03-13
Volume
52
Issue
5
Pages
752-764
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
DOI
10.1007/s00125-009-1313-z
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
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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