Evidence mapPaperPMID 19283361Full record

ReviewDiabetologia2009

The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action.

E J Barrett, E M Eggleston, A C Inyard, H Wang, G Li, W Chai, Z Liu

6 registry-linked trialsOpen access · bronzeAbstract readReview
In one paragraph

Review in Diabetologia, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 6 registered trials, which are not on this map. Cited by 152 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
152citing papers in PubMed, 1 pooled it
14.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

NCT02633488 nacompletedstarted 2014, after this paper: background citation

Effect of Metformin on Insulin Sensitivity and Pan-Arterial Vascular Function in Adults With Metabolic Syndrome

Ran2014Enrolled19Registered outcomes1Posted comparisons1ConditionsInsulin Sensitivity, Metabolic SyndromeArmsMetformin, Placebos
Open the trial in the graph
NCT03883412 phase4recruitingstarted 2019, after this paper: background citation

Effect of Exercise and/or Liraglutide on Vascular Dysfunction and Insulin Sensitivity in Type 2 Diabetes ( ZQL007)

Ran2019Enrolled60Registered outcomes6Posted comparisons0ConditionsType2 DiabetesArmsExercise, liraglutide
Open the trial in the graph
NCT02490124 completednot on this mapstarted 2014, after this paper: background citation

The Effect of Type 1 Diabetes on Pan-Arterial Vascular Function and Insulin Sensitivity in Humans

TypeobservationalSponsorUniversity of VirginiaRan2014 to 2015Enrolled7ConditionsDiabetes Type 1
NCT02628301 nacompletednot on this mapstarted 2015, after this paper: background citation

Is Microvascular Dysfunction an Early Phenomenon in the Development of Skeletal Muscle Insulin Resistance? A Dietary Intervention Study in Healthy Men

TypeinterventionalSponsorAmsterdam UMC, location VUmcRan2015 to 2017Enrolled20ConditionsInsulin Resistance, Type 2 Diabetes, ObesityArmsHypercaloric diet, Normocaloric diet
NCT03174288 nacompletednot on this mapstarted 2015, after this paper: background citation

The Impact of Fitness and Mineralocorticoid Receptor Blockade on Vascular Dysfunction in Adults With Type 1 Diabetes

TypeinterventionalSponsorUniversity of VirginiaRan2015 to 2019Enrolled32ConditionsType 1 DiabetesArmsExercise, Spironolactone
NCT03894527 naunknown statusnot on this mapstarted 2019, after this paper: background citation

Impact of Acute Exercise on Vascular Insulin Sensitivity in Metabolic Syndrome

TypeinterventionalSponsorUniversity of VirginiaRan2019 to 2020Enrolled16ConditionsMetabolic Syndrome, ObesityArmsSingle Bout of Exercise, Control Condition
3 · Its place in the literature

Who cites it

152 citing papers in PubMed, 1 synthesis or guideline pooled it, 315 citations in OpenAlex.

  1. Pooled it
  2. Beneficial vascular effects of oral phosphatidylserine supplementation in type 2 diabetes.Journal of applied physiology (Bethesda, Md. : 1985) · 2026
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  16. Free fatty acids induce insulin resistance in both cardiac and skeletal muscle microvasculature in humans.The Journal of clinical endocrinology and metabolism · 2011 · on this map
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92 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

E J BarrettUniversity of Virginia Health System, Charlottesville, VA 22908, USA. ejb8x@virginia.edu
E M Eggleston
A C Inyard
H Wang
G Li
W Chai
Z Liu
University of Virginia Health System · US

Funding

ZACOPRIDE VS METOCLOPRAMIDE--EFFECT ON LOWER ESOPHAGEAL SPHINCTERM01RR000847 · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · 1985 to 2005
$24.6M
PILOT--PILOT/FEASIBILITY PROGRAMP30DK063609 · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · 2003 to 2005
$3.4M
THE EFFECTS OF INSULIN ON THE MICROVASCULATURER01DK057878 · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · 2001 to 2005
$1.5M
NCRR NIH HHS M01 RR000847NCRR NIH HHS RR00847NIDDK NIH HHS DK-057878NIDDK NIH HHS DK063609NIDDK NIH HHS DK-073759NIDDK NIH HHS P30 DK063609NIDDK NIH HHS R01 DK057878NIDDK NIH HHS R01 DK073759
6 · The paper itself

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.

Indexed as

AnimalsGlucoseGlucose Clamp TechniqueHomeostasisHumansHyperinsulinismInsulinInsulin ResistanceKineticsMicrocirculationMicrodialysisMuscle, SkeletalGlucoseInsulin

Identifiers

PMID19283361
PMCPMC2704146
OpenAlexW2033746638

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

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 Socratic graph.