ArticleThe Journal of clinical investigation2003
Acceleration of type 1 diabetes mellitus in proinsulin 2-deficient NOD mice.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 217 citations in OpenAlex.
- Strategic Reduction of Hybrid Insulin Peptide Formation Significantly Delays Diabetes Onset in NOD Mice.Diabetes · 2026Article
- Crinophagic granules in pancreatic β cells contribute to mouse autoimmune diabetes by diversifying pathogenic epitope repertoire.Nature communications · 2024Article
- Human insulin as both antigen and protector in type 1 diabetes.European journal of immunology · 2024Article
- Islet-specific CD8Immunology and cell biology · 2023Article
- β-Cell Cre Expression and Reduced Ins1 Gene Dosage Protect Mice From Type 1 Diabetes.Endocrinology · 2022Article
- Preclinical Models to Evaluate the Human Response to Autoantigen and Antigen-Specific Immunotherapy in Human Type 1 Diabetes.Frontiers in endocrinology · 2022Review
- Environmental Triggering of Type 1 Diabetes Autoimmunity.Frontiers in endocrinology · 2022Review
- The dark side of insulin: A primary autoantigen and instrument of self-destruction in type 1 diabetes.Molecular metabolism · 2021Review
- Noncontiguous T cell epitopes in autoimmune diabetes: From mice to men and back again.The Journal of biological chemistry · 2021Review
- Altered selection on a single self-ligand promotes susceptibility to organ-specific T cell infiltration.The Journal of experimental medicine · 2021Article
- Oral Fc-Coupled Preproinsulin Achieves Systemic and Thymic Delivery Through the Neonatal Fc Receptor and Partially Delays Autoimmune Diabetes.Frontiers in immunology · 2021Article
- A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes.Frontiers in immunology · 2021Article
- Tolerance to Proinsulin-1 Reduces Autoimmune Diabetes in NOD Mice.Frontiers in immunology · 2021Article
- Tissue-specific autoimmunity controlled by Aire in thymic and peripheral tolerance mechanisms.International immunology · 2020Article
- The presentation of neuroendocrine self-peptides in the thymus: an essential event for individual life and vertebrate survival.Annals of the New York Academy of Sciences · 2019Review
- Transplantation of MHC-mismatched mouse embryonic stem cell-derived thymic epithelial progenitors and MHC-matched bone marrow prevents autoimmune diabetes.Stem cell research & therapy · 2019Article
- The Immunoreactive Platform of the Pancreatic Islets Influences the Development of Autoreactivity.Diabetes · 2019Article
- Article
- Transgenic substitution with Greater Amberjack Seriola dumerili fish insulin 2 in NOD mice reduces beta cell immunogenicity.Scientific reports · 2019Article
- Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence favors a role for proinsulin as a key autoantigen in diabetes. In the mouse, two proinsulin isoforms coexist. Most studies point to proinsulin 2 as the major isoform recognized by T cells in the NOD mouse. We studied mice in which a null proinsulin 2 mutation was transferred from proinsulin 2-deficient 129 mice onto the NOD background along with 16 genetic markers (including I-A(g7) MHC molecule) associated with diabetes. Intercross mice from the fourth backcross generation showed that proinsulin 2(-/-) mice develop accelerated insulitis and diabetes. The high prevalence of anti-insulin autoantibodies in proinsulin 2(-/-) mice indicates that diabetes acceleration relates to altered recognition of proinsulin. The prevalence of anti-glutamic acid decarboxylase autoantibodies and of sialitis is not increased in proinsulin 2(-/-) mice. We give evidence that proinsulin 2 expression leads to silencing of T cells specific for an epitope shared by proinsulin 1 and proinsulin 2. In the human, alleles located in the VNTR region flanking the insulin gene control beta cell response to glucose and proinsulin expression in the thymus and are key determinants of diabetes susceptibility. Proinsulin 2(-/-) NOD mice provide a model to study the role of thymic expression of insulin in susceptibility to diabetes.
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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.