Evidence map›Paper›PMID 29776406›Full record

ArticleCardiovascular diabetology2018

The effect of DPP-4 inhibition to improve functional outcome after stroke is mediated by the SDF-1α/CXCR4 pathway.

Fausto Chiazza, Harald Tammen, Hiranya Pintana, Grazyna Lietzau, Massimo Collino, Thomas Nyström, Thomas Klein, Vladimer Darsalia, Cesare Patrone

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular diabetology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07241897 (DPP4 Inhibitor on Post-stroke Cognitive Impairment in Ischemic Stroke Patients With Type 2 Diabetes Mellitus), which is not on this map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
5.9field-weighted citation impact, top 3% 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.

NCT07241897 phase3not yet recruitingnot on this mapstarted 2025, after this paper: background citation

DPP4 Inhibitor on Post-stroke Cognitive Impairment in Ischemic Stroke Patients With Type 2 Diabetes Mellitus (DISC-DM): Multicentre, Double Blind, Randomised, Placebo Controlled Trial

TypeinterventionalSponsorSecond Affiliated Hospital of Soochow UniversityRan2025 to 2028Enrolled312ConditionsIschemic Stroke, Diabete MellitusArmsSentagliptin Phosphate - single dose, Placebo
3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 57 citations in OpenAlex.

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  15. Pleiotropic Benefits of DPP-4 Inhibitors Beyond Glycemic Control.Clinical medicine insights. Endocrinology and diabetes · 2021
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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

9 authors at 4 institutions in 3 countries.

Fausto ChiazzaDepartment of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83, Stockholm, Sweden. fausto.chiazza@ki.se.
Harald TammenPXBioVision GmbH, Hannover, Germany.
Hiranya PintanaDepartment of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83, Stockholm, Sweden.
Grazyna LietzauDepartment of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83, Stockholm, Sweden.
Massimo CollinoDepartment of Drug Science and Technology, University of Turin, Torino, Italy.
Thomas NyströmDepartment of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83, Stockholm, Sweden.
Thomas KleinDepartment of CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
Vladimer DarsaliaDepartment of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83, Stockholm, Sweden. vladimer.darsalia@ki.se.
Cesare PatroneDepartment of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83, Stockholm, Sweden. cesare.patrone@ki.se.ORCID 0000-0003-0470-4606
Karolinska Institutet · SEBoehringer Ingelheim (Germany) · DEPXBioVisioN (Germany) · DEUniversity of Turin · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are approved drugs for the treatment of hyperglycemia in patients with type 2 diabetes. These effects are mainly mediated by inhibiting endogenous glucagon-like peptide-1 (GLP-1) cleavage. Interestingly, gliptins can also improve stroke outcome in rodents independently from GLP1. However, the underlying mechanisms are unknown. Stromal cell-derived factor-1α (SDF-1α) is a DPP-4 substrate and CXCR4 agonist promoting beneficial effects in injured brains. However, SDF-1α involvement in gliptin-mediated neuroprotection after ischemic injury is unproven. We aimed to determine whether the gliptin linagliptin improves stroke outcome via the SDF-1α/CXCR4 pathway, and identify additional effectors behind the efficacy.

methodsMice were subjected to stroke by transient middle cerebral artery occlusion (MCAO). linagliptin was administered for 3 days or 3 weeks from stroke onset. The CXCR4-antagonist AMD3100 was administered 1 day before MCAO until 3 days thereafter. Stroke outcome was assessed by measuring upper-limb function, infarct volume and neuronal survival. The plasma and brain levels of active GLP-1, GIP and SDF-1α were quantified by ELISA. To identify additional gliptin-mediated molecular effectors, brain samples were analyzed by mass spectrometry.

resultsLinagliptin specifically increased active SDF-1α but not glucose-dependent insulinotropic peptide (GIP) or GLP-1 brain levels. Blocking of SDF-1α/CXCR4 pathway abolished the positive effects of linagliptin on upper-limb function and histological outcome after stroke. Moreover, linagliptin treatment after stroke decreased the presence of peptides derived from neurogranin and from an isoform of the myelin basic protein.

conclusionsWe showed that linagliptin improves functional stroke outcome in a SDF-1α/CXCR4-dependent manner. Considering that Calpain activity and intracellular Ca

Indexed as

AnimalsBrainCalcium SignalingChemokine CXCL12Dipeptidyl Peptidase 4Dipeptidyl-Peptidase IV InhibitorsDisease Models, AnimalInfarction, Middle Cerebral ArteryLinagliptinMaleMice, Inbred C57BLMotor ActivityMyelin Basic ProteinNeuroprotective AgentsReceptors, CXCR4Recovery of FunctionChemokine CXCL12Cxcl12 protein, mouseCXCR4 protein, mouseDipeptidyl Peptidase 4Dipeptidyl-Peptidase IV InhibitorsDpp4 protein, mouseLinagliptinMbp protein, mouseMyelin Basic Proteinneuroguidin protein, mouseNeuroprotective AgentsReceptors, CXCR4Repressor ProteinsCXCR4/SDF-1αDiabetesDPP-4 inhibitorsGliptinsLinagliptinMCAOStroke

Identifiers

PMID29776406
PMCPMC5960142
OpenAlexW2805004527

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.