Evidence map›Paper›PMID 12445887›Full record

ArticleCardiovascular research2002

Physiological concentrations of insulin induce endothelin-mediated vasoconstriction during inhibition of NOS or PI3-kinase in skeletal muscle arterioles.

Etto C Eringa, Coen D A Stehouwer, Thomas Merlijn, Nico Westerhof, Pieter Sipkema

Registry-linked trialOpen access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Cardiovascular research, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03883412 (Effect of Exercise and/or Liraglutide on Vascular Dysfunction and Insulin Sensitivity in Type 2 Diabetes), which is not on this map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
1.9field-weighted citation impact, top 15% 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.

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
3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 116 citations in OpenAlex.

  1. Sugar-sweetened soft drink consumption acutely decreases spontaneous baroreflex sensitivity and heart rate variability.American journal of physiology. Regulatory, integrative and comparative physiology · 2021
    Trial
  2. Trial
  3. Trial
  4. Trial
  5. 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
    Trial
  6. Hyperinsulinemia fails to augment ET-1 action in the skeletal muscle vascular bed in vivo in humans.American journal of physiology. Endocrinology and metabolism · 2008
    Trial
  7. Review
  8. Improvement of Vascular Insulin Sensitivity by Ranolazine.International journal of molecular sciences · 2023
    Article
  9. Common metabolic features of hypertension and type 2 diabetes.Hypertension research : official journal of the Japanese Society of Hypertension · 2023
    Review
  10. New insights into mechanisms of endothelial insulin resistance in type 2 diabetes.American journal of physiology. Heart and circulatory physiology · 2022
    Review
  11. Review
  12. Article
  13. Observational
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
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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

5 authors at 1 institution in 1 country.

Etto C EringaLaboratory for Physiology, VU Medical Centre, van der Boechorststraat 7, Amsterdam, The Netherlands.
Coen D A Stehouwer
Thomas Merlijn
Nico Westerhof
Pieter Sipkema
Amsterdam UMC Location Vrije Universiteit Amsterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo determine the roles of nitric oxide, endothelin-1 and phosphatidylinositol 3-kinase (PI3-kinase) in acute responses of isolated rat skeletal muscle arterioles to insulin.

methodsRat cremaster first order arterioles were separated from surrounding tissue, cannulated in a pressure myograph and responses to insulin (4 microU/ml-3.4 mU/ml) were studied without intraluminal blood or flow.

resultsInsulin alone did not significantly affect arteriolar diameter. Non-selective antagonism of endothelin receptors, with PD-142893, uncovered insulin-induced vasodilatation (25+/-8% from baseline at 3.4 mU/ml), which was abolished by inhibition of NO synthesis with N(G)-nitro-L-arginine (L-NA). Inhibition of NO synthesis alone uncovered insulin-induced vasoconstriction at physiological concentrations (21+/-5% from baseline diameter at 34 microU/ml), which was abolished by PD-142893. The NO donor, S-nitroso-N-acetyl-penicillamine (SNAP) inhibited insulin-induced vasoconstriction during NOS inhibition, even at a concentration that did not elicit vasodilatation itself. Inhibition of PI3-kinase, an intracellular mediator of insulin-induced NO production, with wortmannin, also uncovered insulin-induced vasoconstriction (13+/-3% from baseline at 34 microU/ml) that was abolished by PD-142893.

conclusionsInsulin induces both nitric oxide and endothelin-1 activity in rat cremaster first-order arterioles. This study demonstrates for the first time that vasoconstrictive effects of physiological concentrations of insulin during inhibition of NOS activity are mediated by endothelin and that insulin induces endothelin-1-mediated vasoconstriction in isolated skeletal muscle arterioles during inhibition of PI3-kinase. These findings support the hypothesis of altered microvascular reactivity to insulin in conditions of diminished PI3-kinase activity, a prominent feature of insulin resistance.

Indexed as

AnimalsArteriolesCulture TechniquesDose-Response Relationship, DrugEndothelin-1InsulinMaleMicrocirculationMuscle, SkeletalNitric OxideNitric Oxide SynthasePhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsRatsRats, WistarSignal TransductionEndothelin-1InsulinNitric OxideNitric Oxide SynthasePhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase Inhibitors

Identifiers

PMID12445887
OpenAlexW2071686295

What Socratic holds

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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.