Evidence map›Paper›PMID 23011726›Full record

ArticleNeuromolecular medicine2013

The diabetes drug liraglutide ameliorates aberrant insulin receptor localisation and signalling in parallel with decreasing both amyloid-β plaque and glial pathology in a mouse model of Alzheimer's disease.

Caitriona M Long-Smith, Sean Manning, Paula L McClean, Meghan F Coakley, Domhnall J O'Halloran, Christian Holscher, Cora O'Neill

Abstract read
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In one paragraph

Article in Neuromolecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 4 pooled it
4.7field-weighted citation impact, top 5% 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

75 citing papers in PubMed, 4 syntheses or guidelines pooled it, 156 citations in OpenAlex.

  1. Pooled it
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  4. GLP-1 receptor agonists for Parkinson's disease.The Cochrane database of systematic reviews · 2020
    Pooled it
  5. Trial
  6. Brain effect of bariatric surgery in people with obesity.International journal of obesity (2005) · 2022
    Trial
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  8. Diabetes-Associated Cognitive Impairment: Pathophysiology and Emerging Therapies.Annals of clinical and translational neurology · 2026
    Review
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  12. Article
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15 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 3 institutions in 2 countries.

Caitriona M Long-SmithDepartment of Biochemistry, BioSciences Institute, University College Cork, Cork, Ireland.
Sean Manning
Paula L McClean
Meghan F Coakley
Domhnall J O'Halloran
Christian Holscher
Cora O'Neill
University College Cork · IEUniversity of Ulster · GBCork University Hospital · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) has been shown to involve desensitised insulin receptor (IR) signalling. Liraglutide, a novel glucagon-like peptide 1 (GLP-1) analogue that facilitates insulin signalling, is currently approved for use in type 2 diabetes mellitus. In the present study, we show that distinctive alterations in the localisation and distribution of the IR and increased levels of insulin receptor substrate (IRS)-1 phosphorylated at serine 616 (IRS-1 pS(616)), a key marker of insulin resistance, are associated with amyloid-β plaque pathology in the frontal cortex of a mouse model of AD, APPSWE/PS1dE9. Altered IR status in APPSWE/PS1dE9 is most evident in extracellular deposits with the appearance of dystrophic neurites, with significantly increased IRS-1 pS(616) levels detected within neurons and neurites. The IR and IRS-1 pS(616) changes occur in the vicinity of all plaques in the APPSWE/PS1dE9 brain, and a significant upregulation of astrocytes and microglia surround this pathology. We show that liraglutide treatment for 8 weeks at 25 nmol/kg body weight i.p. once daily in 7-month-old mice significantly decreases IR aberrations in conjunction with a concomitant decrease in amyloid plaque load and levels of IRS-1 pS(616). Liraglutide also induces a highly significant reduction in astrocytosis and microglial number associated with both plaques and IR pathology. The amelioration of IR aberrations and attenuation of IRS-1 pS(616) upregulation, plaque and glial activation in APPSWE/PS1dE9 mice treated with liraglutide support the investigation of the therapeutic potential of liraglutide and long-lasting GLP-1 agonists in patients with AD.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsAstrocytesDisease Models, AnimalFemaleFrontal LobeGlucagon-Like Peptide 1Hypoglycemic AgentsInsulin Receptor Substrate ProteinsInsulin ResistanceLiraglutideMaleMiceMice, Inbred C57BLAmyloid beta-PeptidesAmyloid beta-Protein PrecursorGlucagon-Like Peptide 1Hypoglycemic AgentsInsulin Receptor Substrate ProteinsIrs1 protein, mouseLiraglutideNeuroprotective AgentsPresenilin-1PSEN1 protein, humanReceptor, Insulin

Identifiers

PMID23011726
OpenAlexW2022847635

What OpenQuestion holds

Texttitle and abstract
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.