Evidence map›Paper›PMID 25830095›Full record

ArticleMolecular metabolism2015

Enhanced insulin signaling in density-enhanced phosphatase-1 (DEP-1) knockout mice.

Janine Krüger, Sebastian Brachs, Manuela Trappiel, Ulrich Kintscher, Heike Meyborg, Ernst Wellnhofer, Christa Thöne-Reineke, Philipp Stawowy, Arne Östman, Andreas L Birkenfeld and 2 more

Open access · goldAbstract read
In one paragraph

Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

18 citing papers in PubMed, 33 citations in OpenAlex.

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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

12 authors at 4 institutions in 2 countries.

Janine KrügerCenter for Cardiovascular Research/CCR, Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Hessische Str. 3-4, 10115 Berlin, Charité - Universitätsmedizin Berlin, Germany.
Sebastian BrachsCenter for Cardiovascular Research/CCR, Department of Endocrinology, Diabetes and Nutrition, Hessische Str. 3-4, 10115 Berlin, Charité - Universitätsmedizin Berlin, Germany.
Manuela TrappielCenter for Cardiovascular Research/CCR, Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Hessische Str. 3-4, 10115 Berlin, Charité - Universitätsmedizin Berlin, Germany.
Ulrich KintscherCenter for Cardiovascular Research/CCR, Institute of Pharmacology, Hessische Str. 3-4, 10115 Berlin, Charité - Universitätsmedizin Berlin, Germany.
Heike MeyborgDepartment of Medicine/Cardiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Ernst WellnhoferDepartment of Medicine/Cardiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Christa Thöne-ReinekeCenter for Cardiovascular Research/CCR, Department of Experimental Medicine, Hessische Str. 3-4, 10115 Berlin, Charité - Universitätsmedizin Berlin, Germany.
Philipp StawowyDepartment of Medicine/Cardiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Arne ÖstmanCancer Center Karolinska, R8:03, Department of Oncology-Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden.
Andreas L BirkenfeldCenter for Cardiovascular Research/CCR, Department of Endocrinology, Diabetes and Nutrition, Hessische Str. 3-4, 10115 Berlin, Charité - Universitätsmedizin Berlin, Germany.
Frank D BöhmerCenter for Molecular Biomedicine, Institute of Molecular Cell Biology, Universitätsklinikum Jena, Hans-Knöll-Str. 2, 07745 Jena, Germany.
Kai KappertCenter for Cardiovascular Research/CCR, Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Hessische Str. 3-4, 10115 Berlin, Charité - Universitätsmedizin Berlin, Germany.
Deutsches Herzzentrum der Charité · DECharité - Universitätsmedizin Berlin · DEJena University Hospital · DEKarolinska Institutet · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveInsulin resistance can be triggered by enhanced dephosphorylation of the insulin receptor or downstream components in the insulin signaling cascade through protein tyrosine phosphatases (PTPs). Downregulating density-enhanced phosphatase-1 (DEP-1) resulted in an improved metabolic status in previous analyses. This phenotype was primarily caused by hepatic DEP-1 reduction.

methodsHere we further elucidated the role of DEP-1 in glucose homeostasis by employing a conventional knockout model to explore the specific contribution of DEP-1 in metabolic tissues. Ptprj (-/-) (DEP-1 deficient) and wild-type C57BL/6 mice were fed a low-fat or high-fat diet. Metabolic phenotyping was combined with analyses of phosphorylation patterns of insulin signaling components. Additionally, experiments with skeletal muscle cells and muscle tissue were performed to assess the role of DEP-1 for glucose uptake.

resultsHigh-fat diet fed-Ptprj (-/-) mice displayed enhanced insulin sensitivity and improved glucose tolerance. Furthermore, leptin levels and blood pressure were reduced in Ptprj (-/-) mice. DEP-1 deficiency resulted in increased phosphorylation of components of the insulin signaling cascade in liver, skeletal muscle and adipose tissue after insulin challenge. The beneficial effect on glucose homeostasis in vivo was corroborated by increased glucose uptake in skeletal muscle cells in which DEP-1 was downregulated, and in skeletal muscle of Ptprj (-/-) mice.

conclusionTogether, these data establish DEP-1 as novel negative regulator of insulin signaling.

Indexed as

Density-enhanced phosphatase-1DEP-1, density-enhanced phosphatase-1Glucose homeostasisGTT, glucose tolerance testHFD, high-fat dietIL-6, interleukin 6Insulin resistanceInsulin signalingIR, insulin receptorITT, insulin tolerance testKO, knockoutLFD, low-fat dietMCP-1, monocyte chemotactic protein-1PhosphorylationPTP, protein tyrosine phosphataseRER, respiratory exchange ratioRTK, receptor tyrosine kinaseWT, wild-type

Identifiers

PMID25830095
PMCPMC4354926
OpenAlexW2075953239

What OpenQuestion holds

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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.