Evidence map›Paper›PMID 40926119›Full record

ArticleThe EMBO journal2025

Genetic variance in the murine defensin locus modulates glucose homeostasis.

Stewart W C Masson, Rebecca C Simpson, Harry B Cutler, Patrick W Carlos, Oana C Marian, Belinda Yau, Meg Potter, Søren Madsen, Kristen C Cooke, Niamh R Craw and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Fifteen years of the Diversity Outbred mouse model: a review.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Review
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

21 authors.

Stewart W C MassonSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia. stewart.masson@sydney.edu.au.ORCID http://orcid.org/0000-0003-4514-7009
Rebecca C SimpsonCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Harry B CutlerSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-2074-8599
Patrick W CarlosSchool of Chemistry, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.
Oana C MarianCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0001-5629-7884
Belinda YauCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0003-2303-7343
Meg PotterSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.
Søren MadsenSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-1585-7862
Kristen C CookeSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.
Niamh R CrawSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.
Oliver K FullerSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0003-1914-922X
Dylan J HarneySchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-1148-5838
Mark LaranceCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-8579-2267
Gregory J CooneyCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0003-0012-2529
Grant MorahanCentre for Diabetes Research, Harry Perkins Institute of Medical Research, Murdoch, WA, Australia.
Erin R ShanahanSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.
Melkam A KebedeCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0001-9686-7378
Christopher HodgkinsSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-0210-6410
Richard J PayneSchool of Chemistry, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.
Jacqueline StöckliSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.
David E JamesSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia. david.james@sydney.edu.au.ORCID http://orcid.org/0000-0001-5946-5257

Funding

Department of Education and Training | Australian Research Council (ARC) FL200100096Diabetes Australia Y23G-MASS
6 · The paper itself

Abstract

Insulin resistance is a heritable risk factor for many chronic diseases; however, the genetic drivers remain elusive. In seeking these, we performed genetic mapping of insulin sensitivity in 670 chow-fed Diversity Outbred in Australia (DOz) mice and identified a genome-wide significant locus (QTL) on chromosome 8 encompassing 17 defensin genes. By taking a systems genetics approach, we identified alpha-defensin 26 (Defa26) as the causal gene in this region. To validate these findings, we synthesized Defa26 and performed diet supplementation experiments in two mouse strains with distinct endogenous Defa26 expression levels. In the strain with relatively lower endogenous expression (C57BL/6J) supplementation improved insulin sensitivity and reduced gut permeability, while in the strain with higher endogenous expression (A/J) it caused hypoinsulinemia, glucose intolerance and muscle wasting. Based on gut microbiome and plasma bile acid profiling this appeared to be the result of disrupted microbial bile acid metabolism. These data illustrate the danger of single strain over-reliance and provide the first evidence of a link between host-genetics and insulin sensitivity which is mediated by the microbiome.

Indexed as

alpha-DefensinsGenetic VariationGlucoseHomeostasisInsulin ResistanceQuantitative Trait LociAnimalsBile Acids and SaltsGastrointestinal MicrobiomeMaleMiceMice, Inbred C57BLalpha-DefensinsBile Acids and SaltsGlucoseBile AcidsDefensinDiversity OutbredInsulin SensitivityMicrobiome

Identifiers

PMID40926119
PMCPMC12528722

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.