Evidence map›Paper›PMID 40977091›Full record

ArticleProteomics2025

Characterization of Cytokine Treatment on Human Pancreatic Islets by Top-Down Proteomics.

Ashley N Ives, Tyler J Sagendorf, Lorenz Nierves, Tai-Tu Lin, Ercument Dirice, Rohit N Kulkarni, Ljiljana Paša-Tolić, Wei-Jun Qian, James M Fulcher

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 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. The role of chromogranin A cleavage products in onset of type 1 and 2 diabetes.Frontiers in clinical diabetes and healthcare · 2026
    Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Ashley N IvesEnvironmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington, USA.
Tyler J SagendorfBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Lorenz NiervesBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Tai-Tu LinBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Ercument DiriceDepartment of Pharmacology and Medicine, New York Medical College School of Medicine, Valhalla, New York, USA.
Rohit N KulkarniIslet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, Massachusetts, USA.
Ljiljana Paša-TolićEnvironmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington, USA.
Wei-Jun QianBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.ORCID 0000-0002-5393-2827
James M FulcherEnvironmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington, USA.ORCID 0000-0001-9033-3623

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
Robust Mass Spectrometric Protein/Peptide Assays for Type 1 Diabetes Clinical ApplicationsU01DK137113 · NIDDK · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI Wei-Jun Qian, Jun Qu · 2023 to 2026
$3.8M
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
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
NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R01 DK122160NIDDK NIH HHS R01 DK135081NIDDK NIH HHS U01 DK137113NIH HHS R01DK122160NIH HHS R01DK135081NIH HHS U01DK137113
6 · The paper itself

Abstract

Type 1 diabetes (T1D) results from autoimmune-mediated destruction of insulin-producing β cells in the pancreatic islet. This process is modulated by pro-inflammatory cytokine signaling, which has been previously shown to alter protein expression in ex vivo islets. Herein, we applied top-down proteomics to globally evaluate proteoforms from human islets treated with proinflammatory cytokines (interferon-γ and interleukin-1β). We measured 1636 unique proteoforms across six donors and two time points (control and 24 h post-treatment) and observed consistent changes in abundance across the glicentin-related pancreatic polypeptide (GRPP) and major proglucagon fragment regions of glucagon, as well as the LF-19/catestatin and vasostatin-1/2 region of chromogranin-A. We also observe several proteoforms that increase after cytokine-treatment or are exclusively observed after cytokine-treatment, including forms of beta-2 microglobulin (B2M), high-mobility group N2 protein (HMGN2), and chemokine (C-X-C motif) ligands (CXCL). Together, our quantitative results provide a baseline proteoform profile for human islets and identify several proteoforms that may serve as interesting candidate markers for T1D progression or therapeutic intervention. SUMMARY: This work applies a top-down proteomics workflow for the characterization and label-free quantification of proteoforms from human islets in the context of inflammation. The workflow is optimized for challenges unique to the islet proteome including high disulfide-linkage content and frequent truncation events, resulting in many proteoforms < 5kDa. There are limited examples of top-down proteomics characterization of human islets, thus this study provides a baseline characterization of the proteoforms of major hormones including chromogranin-A (CHGA), chromogranin-B/ secretogranin-1 (CHGB/SCG1), chromogranin-C/ secretogranin-2 (CHGC/SCG2), islet amyloid polypeptide (amylin/IAPP), insulin (INS), glucagon (GCG), pancreatic polypeptide prohormone (PPY), somatostatin (SST), and neurosecretory protein VGF (VGF). The quantitative results of proteoform abundances before and after cytokine treatment, which mimics the proinflammatory environment during T1D progression, provides interesting insights on how prohormone processing is altered under a proinflammatory environment.

Indexed as

CytokinesInterferon-gammaInterleukin-1betaIslets of LangerhansProteomeProteomicsAdultDiabetes Mellitus, Type 1HumansCytokinesInterferon-gammaInterleukin-1betaProteomeglucagoninsulinisletprohormone processingtop‐down proteomics

Identifiers

PMID40977091
PMCPMC12716117

What Socratic holds

Textmetadata
LicenceTDM
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.