Evidence map›Paper›PMID 39422717›Full record

ArticleDiabetologia2025

Circulating extracellular vesicle-carried PTP1B and PP2A phosphatases as regulators of insulin resistance.

Sakina Ali, Xavier Vidal-Gómez, Megan Piquet, Luisa Vergori, Gilles Simard, Séverine Dubois, Pierre-Henri Ducluzeau, Pascal Pomiès, Sarah Kamli-Salino, Mirela Delibégovic and 5 more

Abstract read
In one paragraph

Article in Diabetologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. 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

15 authors.

Sakina Ali *SOPAM, U1063, Inserm, UNIV Angers, SFR ICAT, Angers, France.
Xavier Vidal-Gómez *SOPAM, U1063, Inserm, UNIV Angers, SFR ICAT, Angers, France.ORCID http://orcid.org/0000-0002-7640-7996
Megan PiquetSOPAM, U1063, Inserm, UNIV Angers, SFR ICAT, Angers, France.
Luisa VergoriSOPAM, U1063, Inserm, UNIV Angers, SFR ICAT, Angers, France.
Gilles SimardSOPAM, U1063, Inserm, UNIV Angers, SFR ICAT, Angers, France.
Séverine DuboisSOPAM, U1063, Inserm, UNIV Angers, SFR ICAT, Angers, France.
Pierre-Henri DucluzeauService de Médecine Interne, Unité d'Endocrinologie Diabétologie et Nutrition, Centre Hospitalier Universitaire et Faculté de Médecine, Université de Tours, Tours, France.
Pascal PomièsUniversity of Montpellier, PhyMedExp, Inserm, CNRS UMR, Montpellier, France.ORCID http://orcid.org/0000-0002-5301-6087
Sarah Kamli-SalinoAberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.ORCID http://orcid.org/0000-0002-5107-5366
Mirela DelibégovicAberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.ORCID http://orcid.org/0000-0001-6193-3152
Samir HenniCentre Hospitalo-Universitaire d'Angers (CHU), Angers, France.ORCID http://orcid.org/0000-0002-9838-481X
Frédéric GagnadouxSOPAM, U1063, Inserm, UNIV Angers, SFR ICAT, Angers, France.ORCID http://orcid.org/0000-0002-4231-5102
Ramaroson AndriantsitohainaSOPAM, U1063, Inserm, UNIV Angers, SFR ICAT, Angers, France.ORCID http://orcid.org/0000-0002-4770-3585
M Carmen MartínezSOPAM, U1063, Inserm, UNIV Angers, SFR ICAT, Angers, France. carmen.martinez@inserm.fr.ORCID http://orcid.org/0000-0003-3897-7397
Metabol Study Group

Funding

Fondation de France 00096290Fondation pour la Recherche Médicale SPF201809006985
6 · The paper itself

Abstract

aims/hypothesisMetabolic disorders associated with abdominal obesity, dyslipidaemia, arterial hypertension and hyperglycaemia are risk factors for the development of insulin resistance. Extracellular vesicles (EVs) may play an important role in the regulation of metabolic signalling pathways in insulin resistance and associated complications.

methodsCirculating large EVs (lEVs) and small EVs (sEVs) from individuals with (IR group) and without insulin resistance (n-IR group) were isolated and characterised. lEVs and sEVs were administered by i.v. injection to mice and systemic, adipose tissue and liver insulin signalling were analysed. The role of phosphatases was analysed in target tissues and cells.

resultsInjection of lEVs and sEVs from IR participants impaired systemic, adipose tissue and liver insulin signalling in mice, while EVs from n-IR participants had no effect. Moreover, lEVs and sEVs from IR participants brought about a twofold increase in adipocyte size and adipogenic gene expression. EVs from IR participants expressed two types of phosphatases, phosphotyrosine 1 phosphatase (PTP1B) and protein phosphatase 2 (PP2A), IR lEVs being enriched with the active form of PTP1B while IR sEVs mainly carried active PP2A. Blockade of PTP1B activity in IR lEVs fully restored IRS1 and Akt phosphorylation in adipocytes and blunted insulin-induced Akt phosphorylation by inhibition of the macrophage secretome in hepatocytes. Conversely, blockade of PP2A activity in IR sEVs completely prevented insulin resistance in adipocytes and hepatocytes. CONCLUSIONS/

interpretationThese data demonstrate that inhibition of phosphatases carried by EVs from IR participants rescues insulin signalling in adipocytes and hepatocytes and point towards PTP1B and PP2A carried by IR EVs as being novel potential therapeutic targets against insulin resistance in adipose tissue and liver and the development of obesity.

Indexed as

Extracellular VesiclesInsulin ResistanceProtein Phosphatase 2Protein Tyrosine Phosphatase, Non-Receptor Type 1AdipocytesAdipose TissueAdultAnimalsFemaleHumansInsulinLiverMaleMiceMice, Inbred C57BLMiddle AgedInsulinProtein Phosphatase 2Protein Tyrosine Phosphatase, Non-Receptor Type 1PTPN1 protein, humanAdipose tissueExtracellular vesiclesInsulin resistanceLiverPhosphatases

Identifiers

PMID39422717
PMCPMC11663195

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.