Evidence map›Paper›PMID 26010513›Full record

ArticleCNS neuroscience & therapeutics2015

DPP-4 Inhibitor Linagliptin Attenuates Aβ-induced Cytotoxicity through Activation of AMPK in Neuronal Cells.

Edy Kornelius, Chih-Li Lin, Hsiu-Han Chang, Hsin-Hua Li, Wen-Nung Huang, Yi-Sun Yang, Ying-Li Lu, Chiung-Huei Peng, Chien-Ning Huang

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

Article in CNS neuroscience & therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 1 pooled it
6.9field-weighted citation impact, top 2% 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

64 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.

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  5. Vericiguat reduces pyroptosis in rats with coronary microembolization by inhibiting the AMPK/Nrf2/NLRP3 signaling pathway.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025
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4 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

9 authors at 3 institutions in 1 country.

Edy KorneliusDivision of Endocrinology and Metabolism, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
Chih-Li LinInstitute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Hsiu-Han ChangInstitute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Hsin-Hua LiInstitute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Wen-Nung HuangInstitute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Yi-Sun YangDivision of Endocrinology and Metabolism, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
Ying-Li LuDivision of Endocrinology and Metabolism, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
Chiung-Huei PengDivision of Basic Medical Science, Hungkuang University, Taichung, Taiwan.
Chien-Ning HuangDivision of Endocrinology and Metabolism, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
Chung Shan Medical University · TWChung Shan Medical University Hospital · TWHungkuang University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimIt is now clear that insulin signaling has important roles in regulation of neuronal functions in the brain. Dysregulation of brain insulin signaling has been linked to neurodegenerative disease, particularly Alzheimer's disease (AD). In this regard, there is evidence that improvement of neuronal insulin signaling has neuroprotective activity against amyloid β (Aβ)-induced neurotoxicity for patients with AD. Linagliptin is an inhibitor of dipeptidylpeptidase-4 (DPP-4), which improves impaired insulin secretion and insulin downstream signaling in the in peripheral tissues. However, whether the protective effects of linagliptin involved in Aβ-mediated neurotoxicity have not yet been investigated.

methodsIn the present study, we evaluated the mechanisms by which linagliptin protects against Aβ-induced impaired insulin signaling and cytotoxicity in cultured SK-N-MC human neuronal cells.

resultsOur results showed that Aβ impairs insulin signaling and causes cell death. However, linagliptin significantly protected against Aβ-induced cytotoxicity, and prevented the activation of glycogen synthase kinase 3β (GSK3β) and tau hyperphosphorylation by restoring insulin downstream signaling. Furthermore, linagliptin alleviated Aβ-induced mitochondrial dysfunction and intracellular ROS generation, which may be due to the activation of 5' AMP-activated protein kinase (AMPK)-Sirt1 signaling. This upregulation of Sirt1 expression was also observed in diabetic patients with AD coadministration of linagliptin.

conclusionsTaken together, our findings suggest linagliptin can restore the impaired insulin signaling caused by Aβ in neuronal cells, suggesting DPP-4 inhibitors may have therapeutic potential for reducing Aβ-induced impairment of insulin signaling and neurotoxicity in AD pathogenesis.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseAMP-Activated Protein KinasesAmyloid beta-PeptidesCell Line, TumorCell SurvivalChromonesDiabetes MellitusDipeptidyl-Peptidase IV InhibitorsEnzyme InhibitorsFemaleGene Expression Regulation, NeoplasticGlucagon-Like Peptide 1Glycogen Synthase Kinase 3Glycogen Synthase Kinase 3 beta2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-oneAMP-Activated Protein KinasesAmyloid beta-Peptidesamyloid beta-protein (1-42)ChromonesDipeptidyl-Peptidase IV InhibitorsEnzyme InhibitorsGlucagon-Like Peptide 1Glycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGSK3B protein, humanInsulin-Like Growth Factor ILinagliptinMorpholinesPeptide FragmentsReactive Oxygen SpeciesRNA, MessengerSIRT1 protein, humanSirtuin 1SOD1 protein, humanSuperoxide DismutaseSuperoxide Dismutase-1Alzheimer's diseaseAMP-activated protein kinaseAmyloid-βLinagliptinSirtuin 1

Identifiers

PMID26010513
PMCPMC5033019
OpenAlexW1549622883

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.