Evidence map›Paper›PMID 23767959›Full record

ArticleThe Biochemical journal2013

Diacylglycerol kinase θ couples farnesoid X receptor-dependent bile acid signalling to Akt activation and glucose homoeostasis in hepatocytes.

Kai Cai, Marion B Sewer

Open access · greenAbstract read
In one paragraph

Article in The Biochemical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.6field-weighted citation impact, top 31% 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

14 citing papers in PubMed, 24 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

2 authors at 1 institution in 1 country.

Kai CaiSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, 92093-0704, USA.
Marion B Sewer
University of Montana · US

Funding

Nuclear Lipids in SteroidogenesisR01DK084178 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SEWER, MARION B. · 2010 to 2014
$1.4M
NIDDK NIH HHS DK084178NIDDK NIH HHS R01 DK084178
6 · The paper itself

Abstract

DGKs (diacylglycerol kinases) catalyse the conversion of diacylglycerol into PA (phosphatidic acid), a positive modulator of mTOR (mammalian target of rapamycin). We have found that chenodeoxycholic acid and the synthetic FXR (farnesoid X receptor) ligand GW4064 induce the mRNA and protein expression of DGKθ in the HepG2 cell line and in primary human hepatocytes. Reporter gene studies using 1.5 kB of the DGKθ promoter fused to the luciferase gene revealed that bile acids increase DGKθ transcriptional activity. Mutation of putative FXR-binding sites attenuated the ability of GW4046 to increase DGKθ luciferase activity. Consistent with this finding, ChIP (chromatin immunoprecipitation) assays demonstrated that bile acid signalling increased the recruitment of FXR to the DGKθ promoter. Furthermore, GW4064 evoked a time-dependent increase in the cellular concentration of PA. We also found that GW4064 and PA promote the phosphorylation of mTOR, Akt and FoxO1 (forkhead box O1), and that silencing DGKθ expression significantly abrogated the ability of GW4046 to promote the phosphorylation of these PA-regulated targets. DGKθ was also required for bile-acid-dependent decreased glucose production. Taken together, our results establish DGKθ as a key mediator of bile-acid-stimulated modulation of mTORC2 (mTOR complex 2), the Akt pathway and glucose homoeostasis.

Indexed as

Signal TransductionCells, CulturedChenodeoxycholic AcidDiacylglycerol KinaseGene Expression RegulationGene SilencingGenes, ReporterGlucoseHepatocytesHep G2 CellsHumansIsoenzymesIsoxazolesMechanistic Target of Rapamycin Complex 2Multiprotein ComplexesMutationAKT1 protein, humanChenodeoxycholic AcidDiacylglycerol KinaseGlucoseGW 4064IsoenzymesIsoxazolesMechanistic Target of Rapamycin Complex 2Multiprotein ComplexesPhosphatidic AcidsProto-Oncogene Proteins c-aktReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearRecombinant ProteinsTOR Serine-Threonine Kinases

Identifiers

PMID23767959
PMCPMC3976421
OpenAlexW1968332724

What OpenQuestion holds

Textmetadata
LicenceTDM
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.