ArticleDiabetes2022
Cathepsin D Drives the Formation of Hybrid Insulin Peptides Relevant to the Pathogenesis of Type 1 Diabetes.
Article in Diabetes, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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.
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.
Who cites it
37 citing papers in PubMed, 45 citations in OpenAlex.
- Discovery of Post-Translationally Modified Epitopes in Autoimmunity: Someone Has to Fish so Everyone Can Eat.Immunological reviews · 2026Review
- Beta Cell Stress to Epitope Diversification: Post-Translationally Modified Antigens in Type 1 Diabetes.Immunological reviews · 2026Review
- From Disposal to Display: Crinophagy as a β-Cell Source of Neoantigens in Type 1 Diabetes.Immunological reviews · 2026Review
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- Cathepsins as Core Players in Obesity Pathogenesis: Emerging Therapeutic Targets.Biomolecules · 2026Review
- Antigen-specific immunotherapy with a CD4Nature communications · 2026Article
- A novel region of the insulin B9-23 sequence is targeted by a HIP-reactive diabetogenic T cell clone.Frontiers in immunology · 2026Article
- Stress-driven remodeling of antigen presentation and chemokine signaling in pancreatic β-cells: implications for type 1 diabetes.Frontiers in immunology · 2026Review
- Is the NOD mouse a good model for type 1 diabetes?Diabetologia · 2026Review
- Strategic Reduction of Hybrid Insulin Peptide Formation Significantly Delays Diabetes Onset in NOD Mice.Diabetes · 2026Article
- A multi-level machine learning pipeline for prediction and prioritization of hybrid insulin peptides in type 1 diabetes.Frontiers in immunology · 2026Article
- Unraveling Type 1 Diabetes: Integrating Microbiome, Metabolomics, and Immunomodulation for Next-Generation Therapies.International journal of molecular sciences · 2025Review
- Article
- Type 1 Diabetes: A Guide to Autoimmune Mechanisms for Clinicians.Diabetes, obesity & metabolism · 2025Review
- Novel T-Cell Reactivities to Hybrid Insulin Peptides in Islet Autoantibody-Positive At-Risk Individuals.Diabetes · 2025Article
- Disease-modifying pharmacological treatments of type 1 diabetes: Molecular mechanisms, target checkpoints, and possible combinatorial treatments.Pharmacological reviews · 2025Review
- Dysfunctional β-cell autophagy induces β-cell stress and enhances islet immunogenicity.Frontiers in immunology · 2025Article
- Exploring new frontiers in type 1 diabetes through advanced mass-spectrometry-based molecular measurements.Trends in molecular medicine · 2024Review
- Proinsulin C-peptide is a major source of HLA-DQ8 restricted hybrid insulin peptides recognized by human islet-infiltrating CD4PNAS nexus · 2024Article
- CD4Immunity · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Hybrid insulin peptides (HIPs) form in pancreatic β-cells through the formation of peptide bonds between proinsulin fragments and other peptides. HIPs have been identified in pancreatic islets by mass spectrometry and are targeted by CD4 T cells in patients with type 1 diabetes (T1D) as well as by pathogenic CD4 T-cell clones in nonobese diabetic (NOD) mice. The mechanism of HIP formation is currently poorly understood; however, it is well established that proteases can drive the formation of new peptide bonds in a side reaction during peptide bond hydrolysis. Here, we used a proteomic strategy on enriched insulin granules and identified cathepsin D (CatD) as the primary protease driving the specific formation of HIPs targeted by disease-relevant CD4 T cells in T1D. We also established that NOD islets deficient in cathepsin L (CatL), another protease implicated in the formation of disease-relevant HIPs, contain elevated levels of HIPs, indicating a role for CatL in the proteolytic degradation of HIPs. In summary, our data suggest that CatD may be a therapeutic target in efforts to prevent or slow the autoimmune destruction of β-cells mediated by HIP-reactive CD4 T cells in T1D.
Indexed as
Identifiers
What OpenQuestion holds
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.