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
Authors' conclusion
In 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.
Study context
- Population
- Organ donors from nPOD; frozen pancreatic tissuefinal analysis: mAAb+ n=3 vs non-diabetic (ND) n=3
- Participants
- 5 vs 5
- Comparison
- Islet-autoantibody-positive vs non-diabetic donor islets
- AAb+n = 5
- NDn = 5reference
- Outcome
- Islet proteome, mAAb+ vs ND
Methodological detailslaser microdissection, MS-based proteomics, label-free quantification, age- and sex-matched controls, Data deposited in MassIVE, accession no. MSV000090212
- Laser microdissection
- MS-based proteomics
- Label-free quantification
- Age- and sex-matched controls
- Data deposited in MassIVE, accession no. MSV000090212
Main finding
As reported in the abstract
Proteins identified (false discovery rate <1%)
≈4500
Proteins reliably quantified in every islet sample
2165
Proteins significantly different, mAAb+ vs ND (unadjusted p<0.025, q<0.15)
202
≈10%
Further findings
Support from independent datasets
- Proteome changes supported by independent published datasets, incl. cytokine-treated human islet proteomics and single-cell RNA-seq from AAb+ individuals
Original publication
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