Identification of Hybrid Insulin Peptides (HIPs) in Mouse and Human Islets by Mass Spectrometry.
beta cell proteome
hybrid insulin peptide (HIP)
mass spectrometry
pancreatic islets
type 1 diabetes (T1D)
Journal
Journal of proteome research
ISSN: 1535-3907
Titre abrégé: J Proteome Res
Pays: United States
ID NLM: 101128775
Informations de publication
Date de publication:
01 03 2019
01 03 2019
Historique:
pubmed:
27
12
2018
medline:
29
5
2020
entrez:
27
12
2018
Statut:
ppublish
Résumé
We recently discovered hybrid insulin peptides (HIPs) as a novel class of post-translationally modified peptides in murine-derived beta cell tumors, and we demonstrated that these molecules are autoantigens in type 1 diabetes (T1D). A HIP consists of an insulin fragment linked to another secretory granule peptide via a peptide bond. We verified that autoreactive CD4 T cells in both mouse and human autoimmune diabetes recognize these modified peptides. Here, we use mass spectrometric analyses to confirm the presence of HIPs in both mouse and human pancreatic islets. We also present criteria for the confident identification of these peptides. This work supports the hypothesis that HIPs are autoantigens in human T1D and provides a foundation for future efforts to interrogate this previously unknown component of the beta cell proteome.
Identifiants
pubmed: 30585061
doi: 10.1021/acs.jproteome.8b00875
pmc: PMC7597855
mid: NIHMS1634603
doi:
Substances chimiques
Autoantigens
0
Insulin
0
Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
814-825Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK081166
Pays : United States
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