Evidence map›Paper›PMID 40457096›Full record

ArticleDiabetologia2025

Increased inflammation as well as decreased endoplasmic reticulum stress and translation differentiate pancreatic islets from donors with pre-symptomatic stage 1 type 1 diabetes and non-diabetic donors.

Adam C Swensen, Paul D Piehowski, Jing Chen, X'avia Y Chan, Shane S Kelly, Vladislav A Petyuk, Ronald J Moore, Lith Nasif, Elizabeth A Butterworth, Mark A Atkinson and 4 more

Abstract read
In one paragraph

Article in Diabetologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Adam C Swensen *Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Paul D Piehowski *Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Jing Chen *Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
X'avia Y ChanBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Shane S KellyBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Vladislav A PetyukBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Ronald J MooreBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Lith NasifDepartment of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
Elizabeth A ButterworthDepartment of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
Mark A AtkinsonDepartment of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.ORCID http://orcid.org/0000-0001-8489-4782
Rohit N KulkarniSection of Islet Cell Biology and Regenerative Medicine, Joslin Diabetes Center; Department of Medicine, Beth Israel Deaconess Medical Center; Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5029-6119
Martha Campbell-ThompsonDepartment of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.ORCID http://orcid.org/0000-0001-6878-1235
Clayton E MathewsDepartment of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA. cxm@ufl.edu.ORCID http://orcid.org/0000-0002-8817-6355
Wei-Jun QianBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA. Weijun.qian@pnnl.gov.ORCID http://orcid.org/0000-0002-5393-2827

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
Project 3P01AI042288 · NIAID · UNIVERSITY OF FLORIDA · PI Todd Michael Brusko · 1997 to 2026
$32.9M
Role of IGF-1 and Insulin Receptors Beta-Cell SurvivalR01DK067536 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 2004 to 2026
$8.0M
Organ Specific ProjectU54DK127823 · NIDDK · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI MATHEWS, CLAYTON E · 2020 to 2023
$5.1M
Pathways and Regulators Driving Progressive Islet Cell Dysfunction in Type 1 DiabetesR01DK122160 · NIDDK · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI ROHIT N. KULKARNI, CLAYTON E MATHEWS · 2019 to 2026
$3.7M
Genetic Regulation of Human Beta Cell DestructionUC4DK104194 · NIDDK · UNIVERSITY OF FLORIDA · PI MATHEWS, CLAYTON E · 2014 to 2014
$3.1M
Discovery and Roles of In Situ Islet Neoantigens in Human Type 1 DiabetesR01DK135081 · NIDDK · UNIVERSITY OF FLORIDA · PI CLAYTON E MATHEWS, DAVID A OSTROV · 2023 to 2026
$2.8M
Regulatory Networks and Biomarkers of Beta-cell Dysfunction and ApoptosisUC4DK104167 · NIDDK · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI KULKARNI, ROHIT N., MATHEWS, CLAYTON E · 2014 to 2016
$2.7M
Understanding pancreatic endocrine and exocrine loss in pre-type 1 diabetesR01DK123329 · NIDDK · UNIVERSITY OF FLORIDA · PI CAMPBELL-THOMPSON, MARTHA, HALLER, MICHAEL JAMES · 2020 to 2024
$2.6M
Defining Islet Heterogeneity Using Single Islet TranscriptomicsUC4DK104155 · NIDDK · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI CAMPBELL-THOMPSON, MARTHA, GERLING, IVAN C · 2014 to 2014
$1.6M
Leica Laser Microdissection Microscope for a Shared ResourceS10OD016350 · OD · UNIVERSITY OF FLORIDA · PI CAMPBELL-THOMPSON, MARTHA · 2013 to 2013
$252k
National Institute of Allergy and Infectious Diseases P01AI04228NIAID NIH HHS P01 AI042288NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R01 DK067536NIDDK NIH HHS R01 DK122160NIDDK NIH HHS R01DK122160NIDDK NIH HHS R01 DK123329NIDDK NIH HHS R01DK123329NIDDK NIH HHS R01 DK135081NIDDK NIH HHS R01DK67536NIDDK NIH HHS U54 DK127823NIDDK NIH HHS U54DK127823NIDDK NIH HHS UC4 DK104155NIDDK NIH HHS UC4DK104155NIDDK NIH HHS UC4 DK104167NIDDK NIH HHS UC4 DK104194NIH HHS S10 OD016350
6 · The paper itself

Abstract

aims/hypothesisProgression to type 1 diabetes is associated with genetic factors, the presence of autoantibodies and a decline in beta cell insulin secretion in response to glucose. Very little is known regarding the molecular changes that occur in human insulin-secreting beta cells prior to the onset of type 1 diabetes. Herein, we applied an unbiased proteomics approach to identify changes in proteins and potential mechanisms of islet dysfunction in islet-autoantibody-positive organ donors with pre-symptomatic stage 1 type 1 diabetes (HbA

methodsMultiple islet sections were collected through laser microdissection of frozen pancreatic tissues from organ donors positive for single or multiple islet autoantibodies (AAb

resultsAnalyses resulted in ~4500 proteins identified with low false discovery rate (<1%), with 2165 proteins reliably quantified in every islet sample. We observed large inter-donor variations that presented a challenge for statistical analysis of proteome changes between donor groups. We therefore focused on only the donors with stage 1 type 1 diabetes who were positive for multiple autoantibodies (mAAb CONCLUSIONS/

interpretationIn situ human islet proteome alterations in stage 1 type 1 diabetes centred around several major functional categories, including an expected increase in immune response genes (elevated antigen presentation/HLA), with decreases in protein synthesis and ER stress response, as well as compensatory metabolic response. The dataset serves as a proteomics resource for future studies on beta cell changes during type 1 diabetes progression and pathogenesis. DATA AVAILABILITY: The LC-MS raw datasets that support the findings of this study have been deposited in the online repository: MassIVE ( https://massive.ucsd.edu/ProteoSAFe/static/massive.jsp ) with accession no. MSV000090212.

Indexed as

Diabetes Mellitus, Type 1Endoplasmic Reticulum StressInflammationIslets of LangerhansAdultAutoantibodiesFemaleHumansInsulin-Secreting CellsMaleMiddle AgedProteomicsTissue DonorsYoung AdultAutoantibodiesAutoantibody-positiveBeta cellsHuman isletsIslet proteomeLaser microdissectionMass spectrometryNPODPrediabetesProteomics

Identifiers

PMID40457096
PMCPMC12177028

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.