Evidence map›Paper›PMID 39648458›Full record

ArticleProteomics2025

Reduction of Chemokine CXCL9 Expression by Omega-3 Fatty Acids via ADP-Ribosylhydrolase ARH3 in MIN6 Insulin-Producing Cells.

Youngki You, Soumyadeep Sarkar, Cailin Deiter, Emily C Elliott, Carrie D Nicora, Raghavendra G Mirmira, Lori Sussel, Ernesto S Nakayasu

Abstract read
In one paragraph

Article in Proteomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Youngki YouBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Soumyadeep SarkarBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Cailin DeiterBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical Center, Aurora, Colorado, USA.
Emily C ElliottBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Carrie D NicoraBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Raghavendra G MirmiraKovler Diabetes Center and Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
Lori SusselBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical Center, Aurora, Colorado, USA.
Ernesto S NakayasuBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.ORCID 0000-0002-4056-2695

Funding

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
University of Colorado Anschutz Medical Campus DRCP30DK116073 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI LORI SUSSEL · 2020 to 2026
$10.8M
Transcriptional Mechanisms Governing Beta Cell DifferentiationR01DK060581 · NIDDK · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Raghavendra G Mirmira · 2002 to 2026
$8.5M
Regulation of Pancreatic Islet Cell FateR01DK082590 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI LORI SUSSEL · 2009 to 2026
$7.3M
The Integrated Stress Response in Human Islets During Early T1DU01DK127786 · NIDDK · UNIVERSITY OF CHICAGO · PI EVANS-MOLINA, CARMELLA, MIRMIRA, RAGHAVENDRA G · 2020 to 2025
$7.1M
Alternative RNA splicing events contribute to the onset of islet dysfunction in T1DU01DK127505 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI NAKAYASU, ERNESTO SATOSHI, SUSSEL, LORI · 2020 to 2023
$2.9M
Systematic validation of biomarkers predictive of IA and T1D and their relationship with disease developmentR01DK138335 · NIDDK · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI Thomas O Metz, Ernesto Satoshi Nakayasu · 2024 to 2026
$1.9M
PTPN2 mutations affect islet beta cell susceptibility in T1DR01DK125360 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI SUSSEL, LORI · 2020 to 2023
$1.7M
NIDDK NIH HHS P30 DK116073NIDDK NIH HHS R01 DK060581NIDDK NIH HHS R01 DK082590NIDDK NIH HHS R01 DK125360NIDDK NIH HHS R01 DK138335NIDDK NIH HHS U01 DK127505NIDDK NIH HHS U01 DK127786NIDDK NIH HHS U24 DK104162
6 · The paper itself

Abstract

Type 1 diabetes (T1D) results from the autoimmune destruction of the insulin-producing β cells of the pancreas. Omega-3 fatty acids protect β cells and reduce the incidence of T1D, but the mechanism is poorly understood. We have shown that omega-3 fatty acids reduce pro-inflammatory cytokine-mediated β-cell apoptosis by upregulating the expression of the ADP-ribosylhydrolase ARH3. Here, we further investigate the β-cell protection mechanism of ARH3 by performing siRNA analysis of its gene Adprhl2 in MIN6 insulin-producing cells, subsequent treatment with a cocktail of the pro-inflammatory cytokines IL-1β + IFN-γ + TNF-α, followed by proteomics analysis. ARH3 regulated proteins from several pathways related to the nucleus (splicing, RNA surveillance, and nucleocytoplasmic transport), mitochondria (metabolic pathways), and endoplasmic reticulum (protein folding). ARH3 also regulated the levels of proteins related to antigen processing and presentation, and the chemokine-signaling pathway. We further studied the role of ARH3 in regulating the chemokine CXCL9. We found that ARH3 reduces the cytokine-induced expression of CXCL9, which is dependent on omega-3 fatty acids. In conclusion, we demonstrate that omega-3 fatty acids regulate CXCL9 expression via ARH3, which may have a role in protecting β cells from immune attack thereby preventing T1D development. Significance of the Study: Omega-3 fatty acids have a variety of health benefits. In type 1 diabetes, omega-3 fatty acids reduce the islet autoimmune response and the disease development. Here, we studied the pathways regulated by the adenosine diphosphate (ADP)-ribosylhydrolase ARH3, a protein whose expression is regulated by omega-3 fatty acids. We showed that ARH3 reduces the expression of chemokines in response to omega-3 fatty acids. This represents an anti-inflammatory mechanism of omega-3 fatty acids that might be involved with protection against type 1 diabetes development.

Indexed as

Fatty Acids, Omega-3Insulin-Secreting CellsAnimalsCell LineDiabetes Mellitus, Type 1MiceProteomicsSignal TransductionFatty Acids, Omega-3

Identifiers

PMID39648458
PMCPMC11794668

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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.