Evidence mapPaperPMID 12925848Full record

ArticleNature medicine2003

Glucagon-like peptide-1 receptor is involved in learning and neuroprotection.

Matthew J During, Lei Cao, David S Zuzga, Jeremy S Francis, Helen L Fitzsimons, Xiangyang Jiao, Ross J Bland, Matthias Klugmann, William A Banks, Daniel J Drucker and 1 more

4 registry-linked trialsAbstract read
PubMed Publisher
In one paragraph

Article in Nature medicine, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 351 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
351citing papers in PubMed, 4 pooled it
10.6field-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.

NCT06072963 phase2recruitingstarted 2024, after this paper: background citation

Combination of Intranasal Insulin With Oral Semaglutide to Improve Cognition and Cerebral Blood Flow: a Feasibility Study

Ran2024Enrolled80Registered outcomes15Posted comparisons0ConditionsAlzheimer Disease, Metabolic Syndrome, Mild Cognitive ImpairmentArmsIntranasal insulin, Intranasal insulin placebo, semaglutide, Semaglutide placebo
Open the trial in the graph
NCT00256256 nacompletednot on this mapstarted 2005, after this paper: background citation

The Effect of GLP-1 on Glucose Uptake in the CNS and Heart in Healthy Subjects During Normoglycaemia Assessed by Positron Emission Tomografi

TypeinterventionalSponsorUniversity of AarhusRan2005 to 2007Enrolled10ConditionsType 2 Diabetes, Stroke, Myocardial InfarctionArmsglucagon-like-peptide-1
NCT01469351 nacompletednot on this mapstarted 2012, after this paper: background citation

Neurodegenerative Changes in Alzheimer's Disease: Identifying Potential Effects of Liraglutide on Degenerative Changes

TypeinterventionalSponsorUniversity of AarhusRan2012 to 2013Enrolled34ConditionsAlzheimers DiseaseArmsLiraglutide, non-active study drug
NCT02847403 phase3unknown statusnot on this mapstarted 2016, after this paper: background citation

Long-acting Exenatide: a Tool to Stop Cognitive Decline in Dysglycemic Patients With Mild Cognitive Impairment?

TypeinterventionalSponsorAzienda Ospedaliero-Universitaria di ParmaRan2016 to 2021Enrolled40ConditionsDysglycemia, Cognitive DeficitArmsExenatide, placebo
3 · Its place in the literature

Who cites it

351 citing papers in PubMed, 4 syntheses or guidelines pooled it, 836 citations in OpenAlex.

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  15. Peptide-Incorporated Biomaterials Promote Regeneration of Peripheral Nerve Injuries.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
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  17. Unravelling the novel insights between miR-7 and Parkinson's disease (PD).Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Review
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291 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 3 countries.

Matthew J DuringDepartment of Molecular Medicine and Pathology, University of Auckland, Private Bag 92019, Auckland 86716, New Zealand. m.during@auckland.ac.nz
Lei Cao
David S Zuzga
Jeremy S Francis
Helen L Fitzsimons
Xiangyang Jiao
Ross J Bland
Matthias Klugmann
William A Banks
Daniel J Drucker
Colin N Haile
Jefferson College · USUniversity of Auckland · NZGeriatric Research Education and Clinical Center · USUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glucagon-like peptide-1 (GLP-1) is a gut peptide that, together with its receptor, GLP-1R, is expressed in the brain. Here we show that intracerebroventricular (i.c.v.) GLP-1 and [Ser(2)]exendin(1-9) (HSEGTFTSD; homologous to a conserved domain in the glucagon/GLP-1 family) enhance associative and spatial learning through GLP-1R. [Ser(2)]exendin(1-9), but not GLP-1, is also active when administered peripherally. GLP-1R-deficient mice have a phenotype characterized by a learning deficit that is restored after hippocampal Glp1r gene transfer. In addition, rats overexpressing GLP-1R in the hippocampus show improved learning and memory. GLP-1R-deficient mice also have enhanced seizure severity and neuronal injury after kainate administration, with an intermediate phenotype in heterozygotes and phenotypic correction after Glp1r gene transfer in hippocampal somatic cells. Systemic administration of [Ser(2)]exendin(1-9) in wild-type animals prevents kainate-induced apoptosis of hippocampal neurons. Brain GLP-1R represents a promising new target for both cognitive-enhancing and neuroprotective agents.

Indexed as

Administration, IntranasalAmino Acid SequenceAnimalsApoptosisBehavior, AnimalCognitionGene ExpressionGene Transfer TechniquesGlucagonGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorHippocampusKainic AcidLearningMaleMiceexendin (1-9), Ser(2)-Glp1r protein, mouseGlp1r protein, ratGlucagonGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorKainic AcidNeuroprotective AgentsPeptide FragmentsProtein PrecursorsReceptors, Glucagon

Identifiers

PMID12925848
OpenAlexW2124852816

What Socratic holds

Textmetadata
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.