The dark side of insulin: A primary autoantigen and instrument of self-destruction in type 1 diabetes
Background: Since its discovery 100 years ago, insulin, as the ‘cure’ for type 1 diabetes, has rescued the lives of countless individuals. As the century unfolded and the autoimmune nature of type 1 diabetes was recognised, a darker side of insulin emerged. Autoimmunity to insulin was found to be an...
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-10-01
|
| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877821001332 |
| _version_ | 1828929364358594560 |
|---|---|
| author | Leonard C. Harrison |
| author_facet | Leonard C. Harrison |
| author_sort | Leonard C. Harrison |
| collection | DOAJ |
| description | Background: Since its discovery 100 years ago, insulin, as the ‘cure’ for type 1 diabetes, has rescued the lives of countless individuals. As the century unfolded and the autoimmune nature of type 1 diabetes was recognised, a darker side of insulin emerged. Autoimmunity to insulin was found to be an early marker of risk for type 1 diabetes in young children. In humans, it remains unclear if autoimmunity to insulin is primarily due to a defect in the beta cell itself or to dysregulated immune activation. Conversely, it may be secondary to beta-cell damage from an environmental agent (e.g., virus). Nevertheless, direct, interventional studies in non-obese diabetic (NOD) mouse models of type 1 diabetes point to a critical role for (pro)insulin as a primary autoantigen that drives beta cell pathology. Scope of review: Modelled on Koch's postulates for the pathogenicity of an infectious agent, evidence for a pathogenic role of (pro)insulin as an autoantigen in type 1 diabetes, particularly applicable to the NOD mouse model, is reviewed. Evidence in humans remains circumstantial. Additionally, as (pro)insulin is a target of autoimmunity in type 1 diabetes, its application as a therapeutic tool to elicit antigen-specific immune tolerance is assessed. Major conclusions: Paradoxically, insulin is both a ‘cure’ and a potential ‘cause’ of type 1 diabetes, actively participating as an autoantigen to drive autoimmune destruction of beta cells - the instrument of its own destruction. |
| first_indexed | 2024-12-14T00:17:52Z |
| format | Article |
| id | doaj.art-2921e98939dd4f4fb95c41fbb9180295 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-14T00:17:52Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-2921e98939dd4f4fb95c41fbb91802952022-12-21T23:25:24ZengElsevierMolecular Metabolism2212-87782021-10-0152101288The dark side of insulin: A primary autoantigen and instrument of self-destruction in type 1 diabetesLeonard C. Harrison0Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC, 3010, Australia; Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, 3052, Australia.Background: Since its discovery 100 years ago, insulin, as the ‘cure’ for type 1 diabetes, has rescued the lives of countless individuals. As the century unfolded and the autoimmune nature of type 1 diabetes was recognised, a darker side of insulin emerged. Autoimmunity to insulin was found to be an early marker of risk for type 1 diabetes in young children. In humans, it remains unclear if autoimmunity to insulin is primarily due to a defect in the beta cell itself or to dysregulated immune activation. Conversely, it may be secondary to beta-cell damage from an environmental agent (e.g., virus). Nevertheless, direct, interventional studies in non-obese diabetic (NOD) mouse models of type 1 diabetes point to a critical role for (pro)insulin as a primary autoantigen that drives beta cell pathology. Scope of review: Modelled on Koch's postulates for the pathogenicity of an infectious agent, evidence for a pathogenic role of (pro)insulin as an autoantigen in type 1 diabetes, particularly applicable to the NOD mouse model, is reviewed. Evidence in humans remains circumstantial. Additionally, as (pro)insulin is a target of autoimmunity in type 1 diabetes, its application as a therapeutic tool to elicit antigen-specific immune tolerance is assessed. Major conclusions: Paradoxically, insulin is both a ‘cure’ and a potential ‘cause’ of type 1 diabetes, actively participating as an autoantigen to drive autoimmune destruction of beta cells - the instrument of its own destruction.http://www.sciencedirect.com/science/article/pii/S2212877821001332Beta cellInsulinAutoantigenAutoantibodyT cellImmune tolerance |
| spellingShingle | Leonard C. Harrison The dark side of insulin: A primary autoantigen and instrument of self-destruction in type 1 diabetes Molecular Metabolism Beta cell Insulin Autoantigen Autoantibody T cell Immune tolerance |
| title | The dark side of insulin: A primary autoantigen and instrument of self-destruction in type 1 diabetes |
| title_full | The dark side of insulin: A primary autoantigen and instrument of self-destruction in type 1 diabetes |
| title_fullStr | The dark side of insulin: A primary autoantigen and instrument of self-destruction in type 1 diabetes |
| title_full_unstemmed | The dark side of insulin: A primary autoantigen and instrument of self-destruction in type 1 diabetes |
| title_short | The dark side of insulin: A primary autoantigen and instrument of self-destruction in type 1 diabetes |
| title_sort | dark side of insulin a primary autoantigen and instrument of self destruction in type 1 diabetes |
| topic | Beta cell Insulin Autoantigen Autoantibody T cell Immune tolerance |
| url | http://www.sciencedirect.com/science/article/pii/S2212877821001332 |
| work_keys_str_mv | AT leonardcharrison thedarksideofinsulinaprimaryautoantigenandinstrumentofselfdestructionintype1diabetes AT leonardcharrison darksideofinsulinaprimaryautoantigenandinstrumentofselfdestructionintype1diabetes |