Evidence map›Paper›PMID 32298772›Full record

ArticleMolecular metabolism2020

A genetic screen identifies Crat as a regulator of pancreatic beta-cell insulin secretion.

Dassine Berdous, Xavier Berney, Ana Rodriguez Sanchez-Archidona, Maxime Jan, Clara Roujeau, Isabel C Lopez-Mejia, Randall Mynatt, Bernard Thorens

Open access · goldAbstract read
In one paragraph

Article in Molecular metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

4 citing papers in PubMed, 8 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

8 authors at 3 institutions in 2 countries.

Dassine BerdousCenter for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland. Electronic address: dassine.berdous@unil.ch.
Xavier BerneyCenter for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland. Electronic address: xavierpascal.berney@unil.ch.
Ana Rodriguez Sanchez-ArchidonaCenter for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland; Vital-IT, Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland. Electronic address: ana.rodriguez.1@unil.ch.
Maxime JanCenter for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland. Electronic address: maxime.jan@unil.ch.
Clara RoujeauCenter for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland. Electronic address: clara.roujeau@unil.ch.
Isabel C Lopez-MejiaCenter for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland. Electronic address: isabel.lopezmejia@unil.ch.
Randall MynattPennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA. Electronic address: Randall.Mynatt@pbrc.edu.
Bernard ThorensCenter for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland. Electronic address: Bernard.thorens@unil.ch.
University of Lausanne · CHPennington Biomedical Research Center · USSIB Swiss Institute of Bioinformatics · CH

Funding

Tracking & Evaluation CoreU54GM104940 · NIGMS · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · PI JUDD E SHELLITO · 2012 to 2026
$69.1M
NIGMS NIH HHS U54 GM104940
6 · The paper itself

Abstract

objectivesGlucose-stimulated insulin secretion is a critical function in the regulation of glucose homeostasis, and its deregulation is associated with the development of type 2 diabetes. Here, we performed a genetic screen using islets isolated from the BXD panel of advanced recombinant inbred (RI) lines of mice to search for novel regulators of insulin production and secretion.

methodsPancreatic islets were isolated from 36 RI BXD lines and insulin secretion was measured following exposure to 2.8 or 16.7 mM glucose with or without exendin-4. Islets from the same RI lines were used for RNA extraction and transcript profiling. Quantitative trait loci (QTL) mapping was performed for each secretion condition and combined with transcriptome data to prioritize candidate regulatory genes within the identified QTL regions. Functional studies were performed by mRNA silencing or overexpression in MIN6B1 cells and by studying mice and islets with beta-cell-specific gene inactivation.

resultsInsulin secretion under the 16.7 mM glucose plus exendin-4 condition was mapped significantly to a chromosome 2 QTL. Within this QTL, RNA-Seq data prioritized Crat (carnitine O-acetyl transferase) as a strong candidate regulator of the insulin secretion trait. Silencing Crat expression in MIN6B1 cells reduced insulin content and insulin secretion by ∼30%. Conversely, Crat overexpression enhanced insulin content and secretion by ∼30%. When islets from mice with beta-cell-specific Crat inactivation were exposed to high glucose, they displayed a 30% reduction of insulin content as compared to control islets. We further showed that decreased Crat expression in both MIN6B1 cells and pancreatic islets reduced the oxygen consumption rate in a glucose concentration-dependent manner.

conclusionsWe identified Crat as a regulator of insulin secretion whose action is mediated by an effect on total cellular insulin content; this effect also depends on the genetic background of the RI mouse lines. These data also show that in the presence of the stimulatory conditions used the insulin secretion rate is directly related to the insulin content.

Indexed as

AnimalsCarnitine O-AcetyltransferaseDiabetes Mellitus, Type 2ExenatideGenetic TestingGlucoseInsulinInsulin-Secreting CellsInsulin SecretionIslets of LangerhansMaleMiceMice, Inbred StrainsQuantitative Trait LociCarnitine O-AcetyltransferaseExenatideGlucoseInsulinBeta-cellsCarnitine acetyltransferaseDiabetesGeneticsInsulin secretionRecombinant inbred mice

Identifiers

PMID32298772
PMCPMC7225740
OpenAlexW3017048360

What Socratic 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 Socratic graph.