Evidence map›Paper›PMID 23011352›Full record

ArticleDiabetologia2012

Treatment of autoimmune diabetes in NOD mice by Toll-like receptor 2 tolerance in conjunction with dipeptidyl peptidase 4 inhibition.

D-H Kim, J-C Lee, M-K Lee, K-W Kim, M-S Lee

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 2 pooled it
4.1field-weighted citation impact, top 6% 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

20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.

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  10. Molecules (Basel, Switzerland) · 2018
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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

5 authors at 2 institutions in 1 country.

D-H KimDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-ku, Seoul, Korea.
J-C Lee
M-K Lee
K-W Kim
M-S Lee
Samsung Medical Center · KRSungkyunkwan University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisWe have shown that chronic administration of the Toll-like receptor 2 (TLR2) agonist Pam3CSK(4) prevents diabetes in NOD mice by inducing TLR2 tolerance of dendritic cells (DCs). We have also reported that a novel dipeptidyl peptidase 4 (DPP4) inhibitor, DA-1229, could increase beta cell mass. Here we investigated whether a combination of DPP4 inhibition, with beneficial effects on beta cell mass, and TLR2 tolerisation, protecting beta cells from autoimmune destruction, could treat a model of established type 1 diabetes.

methodsDiabetic NOD mice were treated with 100 μg Pam3CSK(4), administered three times a week for 3 weeks, in combination with feeding with chow containing 0.3% DA-1229. Beta cell mass and proliferation were studied by immunohistochemistry. DC tolerance was assessed by studying diabetogenic CD4(+) T cell priming after adoptive transfer and expression of costimulatory molecules on DCs by flow cytometry.

resultsWe observed reversal of diabetes in NOD mice by Pam3CSK(4)+DA-1229 but not by either Pam3CSK(4) or DA-1229 alone. Beta cell mass and the number of proliferating beta cells were significantly enhanced by Pam3CSK(4)+DA-1229, but not by either Pam3CSK(4) or DA-1229 alone. Diabetogenic T cell priming by DCs and upregulation of costimulatory molecules after ex vivo stimulation were attenuated in mice treated with Pam3CSK(4)+DA-1229, indicating DC tolerance. The relative proportions of CD4(+) T cells, CD8(+) T cells, B cells, DCs, macrophages and regulatory T cells, and T-helper polarisation were unchanged by treatment with Pam3CSK(4)+DA-1229. CONCLUSIONS/

interpretationThese data demonstrate that a combination of TLR2 tolerisation and DPP4 inhibition can reverse early-onset diabetes in NOD mice.

Indexed as

AnimalsCell DifferentiationDendritic CellsDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1Dipeptidyl-Peptidase IV InhibitorsFemaleFlow CytometryLipopeptidesMaleMiceMice, Inbred NODPiperazinesPrediabetic StateToll-Like Receptor 24-(3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl)piperazin-2-oneDipeptidyl-Peptidase IV InhibitorsLipopeptidesPam(3)CSK(4) peptidePiperazinesToll-Like Receptor 2

Identifiers

PMID23011352
OpenAlexW2099579735

What OpenQuestion holds

Textmetadata
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.