ArticleDiabetes2022
Carbonyl Posttranslational Modification Associated With Early-Onset Type 1 Diabetes Autoimmunity.
Article in Diabetes, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- BAF60A governs beta cell identity to control systemic glucose homeostasis.Diabetologia · 2026Article
- Beta Cell Stress to Epitope Diversification: Post-Translationally Modified Antigens in Type 1 Diabetes.Immunological reviews · 2026Review
- New and emerging therapies in type 1 diabetes mellitus.The Journal of clinical investigation · 2026Review
- Rapid protein carbonylation and decreased insulin secretion induced by inflammatory oxidative stress compounds.Free radical biology & medicine · 2026Article
- Neoepitopes at the crossroads of immunometabolism: metabolic remodeling of antigen presentation in type 1 diabetes.Frontiers in immunology · 2026Review
- Review
- A microenvironment-driven HLA-II-associated insulin neoantigen elicits persistent memory T cell activation in diabetes.Nature immunology · 2026Article
- Modulating immune response for the prevention and treatment of type 1 diabetes.Frontiers in immunology · 2026Review
- Article
- The role of oxidative post-translational modifications in type 1 diabetes pathogenesis.Frontiers in immunology · 2025Review
- Scars of oxidative stress: protein carbonylation and beta cell dysfunction in diabetes.Frontiers in endocrinology · 2025Review
- The immunology of type 1 diabetes.Nature reviews. Immunology · 2024Review
- CD4+ T Cells From Individuals With Type 1 Diabetes Respond to a Novel Class of Deamidated Peptides Formed in Pancreatic Islets.Diabetes · 2024Article
- The Ailing β-Cell in Diabetes: Insights From a Trip to the ER: The 2023 Outstanding Scientific Achievement Award Lecture.Diabetes · 2024Review
- Post-Translational Modifications and Diabetes.Biomolecules · 2024Review
- Breaking tolerance: autoantibodies can target protein posttranslational modifications.Current opinion in biotechnology · 2024Review
- Natural isoaspartyl protein modification of ZAP70 alters T cell responses in lupus.Autoimmunity · 2023Article
- Using mass spectrometry to identify neoantigens in autoimmune diseases: The type 1 diabetes example.Seminars in immunology · 2023Review
- Biomarkers of autoimmunity and beta cell metabolism in type 1 diabetes.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 1 country.
Funding
Abstract
Inflammation and oxidative stress in pancreatic islets amplify the appearance of various posttranslational modifications to self-proteins. In this study, we identified a select group of carbonylated islet proteins arising before the onset of hyperglycemia in NOD mice. Of interest, we identified carbonyl modification of the prolyl-4-hydroxylase β subunit (P4Hb) that is responsible for proinsulin folding and trafficking as an autoantigen in both human and murine type 1 diabetes. We found that carbonylated P4Hb is amplified in stressed islets coincident with decreased glucose-stimulated insulin secretion and altered proinsulin-to-insulin ratios. Autoantibodies against P4Hb were detected in prediabetic NOD mice and in early human type 1 diabetes prior to the onset of anti-insulin autoimmunity. Moreover, we identify autoreactive CD4+ T-cell responses toward carbonyl-P4Hb epitopes in the circulation of patients with type 1 diabetes. Our studies provide mechanistic insight into the pathways of proinsulin metabolism and in creating autoantigenic forms of insulin in type 1 diabetes.
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Registered trials
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.