Evidence mapPaperPMID 35298439Full record

ArticleJCI insight2022

14-3-3ζ Constrains insulin secretion by regulating mitochondrial function in pancreatic β cells.

Yves Mugabo, Cheng Zhao, Ju Jing Tan, Anindya Ghosh, Scott A Campbell, Evgenia Fadzeyeva, Frédéric Paré, Siew Siew Pan, Maria Galipeau, Julia Ast and 5 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

22 citing papers in PubMed, 26 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

15 authors at 6 institutions in 4 countries.

Yves MugaboDepartment of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Cheng ZhaoDivision of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Ju Jing TanDepartment of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Anindya GhoshDepartment of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Scott A CampbellDepartment of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Evgenia FadzeyevaThe University of Ottawa, Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, Ottawa, Ontario, Canada.
Frédéric ParéDepartment of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Siew Siew PanDepartment of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Maria GalipeauDepartment of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Julia AstInstitute of Metabolism and Systems Research (IMSR), Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham, United Kingdom.
Johannes BroichhagenLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Department of Chemical Biology, Berlin, Germany.
David J HodsonInstitute of Metabolism and Systems Research (IMSR), Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham, United Kingdom.
Erin E MulvihillThe University of Ottawa, Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, Ottawa, Ontario, Canada.
Sophie PetropoulosDepartment of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Gareth E LimDepartment of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Centre Hospitalier de l’Université de Montréal · CAKarolinska University Hospital · SENIHR Surgical Reconstruction and Microbiology Research Centre · GBUniversity of Ottawa · CAEspace pour la vie · CALeibniz-Forschungsinstitut für Molekulare Pharmakologie · DE

Funding

Integrated Islet Distribution Program (U24) - 2021U24DK098085 · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2025 to 2025
$3.0M
Medical Research Council MR/N00275X/1Medical Research Council MR/S025618/1NIDDK NIH HHS UC4 DK098085
6 · The paper itself

Abstract

While critical for neurotransmitter synthesis, 14-3-3 proteins are often assumed to have redundant functions due to their ubiquitous expression, but despite this assumption, various 14-3-3 isoforms have been implicated in regulating metabolism. We previously reported contributions of 14-3-3ζ in β cell function, but these studies were performed in tumor-derived MIN6 cells and systemic KO mice. To further characterize the regulatory roles of 14-3-3ζ in β cell function, we generated β cell-specific 14-3-3ζ-KO mice. Although no effects on β cell mass were detected, potentiated glucose-stimulated insulin secretion (GSIS), mitochondrial function, and ATP synthesis were observed. Deletion of 14-3-3ζ also altered the β cell transcriptome, as genes associated with mitochondrial respiration and oxidative phosphorylation were upregulated. Acute 14-3-3 protein inhibition in mouse and human islets recapitulated the enhancements in GSIS and mitochondrial function, suggesting that 14-3-3ζ is the critical isoform in β cells. In dysfunctional db/db islets and human islets from type 2 diabetic donors, expression of Ywhaz/YWHAZ, the gene encoding 14-3-3ζ, was inversely associated with insulin secretion, and pan-14-3-3 protein inhibition led to enhanced GSIS and mitochondrial function. Taken together, this study demonstrates important regulatory functions of 14-3-3ζ in the regulation of β cell function and provides a deeper understanding of how insulin secretion is controlled in β cells.

Indexed as

Insulin-Secreting Cells14-3-3 ProteinsAnimalsGlucoseInsulinInsulin SecretionMiceMitochondria14-3-3 ProteinsGlucoseInsulinAdaptor proteinsBeta cellsEndocrinologyMetabolismMitochondria

Identifiers

PMID35298439
PMCPMC9089799
OpenAlexW4220754864

What Socratic holds

Textmetadata
LicenceCC BY
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.