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Oxidative Post-Translational Modifications of Insulin in Type 1 Diabetes Autoimmunity
Chiara Vinci1, Valentina Franzese2,3,4, Nelig Legoux4
1Center for Diabetes Research, Université Libre de Bruxelles, Brussels, Belgium.
Immunological Reviews
|August 7, 2026
Summary
Oxidative stress modifies insulin in pancreatic beta cells, creating neoantigens that trigger autoimmune responses in type 1 diabetes (T1D). These modified insulin species are key targets for T1D biomarkers and therapies.
Area of Science:
- Immunology
- Endocrinology
- Biochemistry
Background:
- Type 1 diabetes (T1D) involves T cell destruction of pancreatic beta cells.
- Stressed beta cells actively contribute to T1D pathogenesis.
- Oxidative stress in beta cells can modify insulin, forming potential neoantigens.
Purpose of the Study:
- To review mechanisms of oxidatively modified insulin (oxPTM-insulin) generation.
- To summarize evidence for oxPTM-insulin's role in T1D.
- To explore oxPTM-insulin as a biomarker and therapeutic target.
Main Methods:
- Literature review of biochemical and immunological studies.
- Analysis of mechanisms of insulin modification.
- Examination of methodological challenges in identifying modified insulin.
Main Results:
- Beta cells are prone to oxidative protein modification due to high insulin load and stress.
- Insulin undergoes various oxidative and nonenzymatic modifications (oxidation, chlorination, nitration, glycation).
- Oxidatively modified insulin species are recognized by autoantibodies and T cells in T1D patients.
Conclusions:
- Oxidatively modified insulin species (oxPTM-insulin) act as neoantigens in T1D.
- Understanding oxPTM-insulin generation and recognition is crucial for T1D research.
- oxPTM-insulin holds potential as a biomarker and therapeutic target for T1D.
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