Evidence map›Paper›PMID 40112799›Full record

ArticleCell2025

Genetic protection from type 1 diabetes resulting from accelerated insulin mRNA decay.

René van Tienhoven, Denis O'Meally, Tristan A Scott, Kevin V Morris, John C Williams, John S Kaddis, Arnaud Zaldumbide, Bart O Roep

Abstract read
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
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

13 citing papers in PubMed.

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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.

René van TienhovenDepartment of Diabetes Immunology, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.
Denis O'MeallyDepartment of Diabetes and Cancer Discovery Science, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
Tristan A ScottCenter for Gene Therapy, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
Kevin V MorrisCentre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, Brisbane, QLD 4059, Australia.
John C WilliamsDepartment of Molecular Medicine, City of Hope National Medical Center, Duarte, CA 91010, USA.
John S KaddisDepartment of Diabetes and Cancer Discovery Science, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
Arnaud ZaldumbideDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.
Bart O RoepDepartment of Internal Medicine, Leiden University Medical Center, Leiden 2333ZA, the Netherlands. Electronic address: boroep@lumc.nl.

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
Renewal of the Human Islet Research Enhancement Center (HIREC) for the Type-1-Diabetes-Focused Human Islet Research Network (HIRN).U24DK104162 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI John S. Kaddis, Joyce Carol Niland · 2019 to 2026
$12.3M
NCI NIH HHS P30 CA033572NIDDK NIH HHS U24 DK104162
6 · The paper itself

Abstract

Insulin gene (INS) variation and beta-cell stress are associated with the risk of development of type 1 diabetes (T1D) and autoimmunity against insulin. The unfolded protein response alleviating endoplasmic reticulum (ER) stress involves activation of inositol-requiring enzyme 1α (IRE1α) that impedes translation by mRNA decay. We discover that the IRE1α digestion motif is present in insulin mRNA carrying SNP rs3842752 (G>A). This SNP in the 3' untranslated region of INS associates with protection from T1D (INS

Indexed as

Diabetes Mellitus, Type 1InsulinRNA Stability3' Untranslated RegionsAnimalsEndoplasmic Reticulum StressEndoribonucleasesHumansInsulin-Secreting CellsMiceMice, Inbred NODPolymorphism, Single NucleotideProtein Serine-Threonine KinasesRNA, Messenger3' Untranslated RegionsEndoribonucleasesERN1 protein, humanInsulinProtein Serine-Threonine KinasesRNA, Messengerbeta cell functiondefective ribosomal productER stressgenetic riskimmune toleranceimmunogenicityinsulin geneneoantigentype 1 diabetesunfolded protein response

Identifiers

PMID40112799
PMCPMC13689998

What OpenQuestion holds

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Registered trials

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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.