Evidence map›Paper›PMID 11342583›Full record

ArticleThe Journal of clinical investigation2001

Chronic endothelin-1 treatment leads to heterologous desensitization of insulin signaling in 3T3-L1 adipocytes.

K I Ishibashi, T Imamura, P M Sharma, J Huang, S Ugi, J M Olefsky

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.6field-weighted citation impact, top 17% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 95 citations in OpenAlex.

  1. Article
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  13. Article
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  16. Article
  17. Cerebrovascular responses to insulin in rats.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2009
    Article
  18. Parathyroid hormone suppresses insulin signaling in adipocytes.Molecular and cellular endocrinology · 2009
    Article
  19. Article
  20. Review
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

6 authors at 1 institution in 1 country.

K I IshibashiDepartment of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California 92093-0673, USA.
T Imamura
P M Sharma
J Huang
S Ugi
J M Olefsky
University of California, San Diego · US

Funding

INSULIN RECEPTORS AND THE GLUCOSE TRANSPORT SYSTEMR37DK033651 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI OLEFSKY, JERROLD MICHAEL · 2000 to 2010
$6.1M
INSULIN RECEPTORS AND THE GLUCOSE TRANSPORT SYSTEMR01DK033651 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI OLEFSKY, JERROLD MICHAEL · 1986 to 2013
$2.2M
NIDDK NIH HHS DK 33651NIDDK NIH HHS R01 DK033651NIDDK NIH HHS R37 DK033651
6 · The paper itself

Abstract

We recently reported that insulin and endothelin-1 (ET-1) can stimulate GLUT4 translocation via the heterotrimeric G protein G alpha q/11 and through PI3-kinase--mediated pathways in 3T3-L1 adipocytes. Because both hormones stimulate glucose transport through a common downstream pathway, we determined whether chronic ET-1 pretreatment would desensitize these cells to acute insulin signaling. We found that ET-1 pretreatment substantially inhibited insulin-stimulated 2-deoxyglucose uptake and GLUT4 translocation. Cotreatment with the ETA receptor antagonist BQ 610 prevented these effects, whereas inhibitors of G alpha i or G beta gamma were without effect. Chronic ET-1 treatment inhibited insulin-stimulated tyrosine phosphorylation of G alpha q/11 and IRS-1, as well as their association with PI3-kinase and blocked the activation of PI3-kinase activity and phosphorylation of AKT: In addition, chronic ET-1 treatment caused IRS-1 degradation, which could be blocked by inhibitors of PI3-kinase or p70 S6-kinase. Similarly, expression of a constitutively active G alpha q mutant, but not the wild-type G alpha q, led to IRS-1 degradation and inhibited insulin-stimulated phosphorylation of IRS-1, suggesting that the ET-1-induced decrease in IRS-1 depends on G alpha q/11 and PI3-kinase. Insulin-stimulated tyrosine phosphorylation of SHC was also reduced in ET-1 treated cells, resulting in inhibition of the MAPK pathway. In conclusion, chronic ET-1 treatment of 3T3-L1 adipocytes leads to heterologous desensitization of metabolic and mitogenic actions of insulin, most likely through the decreased tyrosine phosphorylation of the insulin receptor substrates IRS-1, SHC, and G alpha q/11.

Indexed as

Muscle ProteinsProtein Serine-Threonine KinasesUbiquitin-Protein Ligases3T3 CellsAdaptor Proteins, Signal TransducingAdipocytesAnimalsBiological TransportDeoxyglucoseDrug InteractionsEndothelin-1Endothelin Receptor AntagonistsGlucose Transporter Type 4GTP-Binding Protein alpha Subunit, Gi2GTP-Binding Protein alpha Subunits, Gi-GoGTP-Binding Protein alpha Subunits, Gq-G11Adaptor Proteins, Signal TransducingBQ 610CBL protein, humanCbl protein, mouseDeoxyglucoseEndothelin-1Endothelin Receptor AntagonistsGab1 protein, mouseGlucose Transporter Type 4Gnai2 protein, mouseGTP-Binding Protein alpha Subunit, Gi2GTP-Binding Protein alpha Subunits, Gi-GoGTP-Binding Protein alpha Subunits, Gq-G11Heterotrimeric GTP-Binding ProteinsInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsIntramolecular TransferasesIrs1 protein, mouseIrs2 protein, mouseMitogen-Activated Protein KinasesMonosaccharide Transport ProteinsMuscle ProteinsOligopeptidesPhosphatidylinositol 3-KinasesPhosphoproteinsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-cblReceptor, Endothelin ASlc2a4 protein, mousesqualene-hopene cyclaseTyrosineUbiquitin-Protein Ligases

Identifiers

PMID11342583
PMCPMC209278
OpenAlexW2065797421

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.