Insulin as a key autoantigen in the development of type 1 diabetes

Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO 80045, USA.
Diabetes/Metabolism Research and Reviews (Impact Factor: 3.55). 11/2011; 27(8):773-7. DOI: 10.1002/dmrr.1250
Source: PubMed


Type 1 diabetes is a T-cell-mediated autoimmune disease against pancreatic beta cells. T cells target various antigens such as insulin, chromogranin A, glutamic acid decarboxylase and islet-specific glucose-6-phosphatase catalytic subunit-related protein. Elimination of insulin dramatically prevents diabetes in the non-obese diabetic (NOD) mouse model and response to insulin occurs prior to that to other antigens. These findings suggest that insulin is a target antigen at the early stage of the disease and is likely to be essential to cause anti-islet autoimmunity in NOD mice. In this review, we discuss whether insulin is truly essential and is only the single essential autoantigen for NOD mice and potentially for man. Although the ultimate principle is still being addressed, it is certain that T-cell response to insulin is a major check point to develop type 1 diabetes in NOD mice. Given multiple similarities between diabetes of NOD mice and man, targeting insulin and insulin-reactive T cells may provide opportunities to develop robust immunotherapies.

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    • "Reviews summarize the results from these studies and indicate that insulin is a primary AAg in the development of T1DM [19] [27]. In NOD knockout and transgenic models, elimination of several islet AAgs and AAg-specific T Figure 1. A. AAg-mediated pancreatic beta cell destruction. "
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    ABSTRACT: Type 1 diabetes mellitus (T1DM) is characterized by recognition of beta cell proteins as self-antigens, called autoantigens (AAgs), by patients' own CD4+ and CD8+ T cells and/or the products of self-reactive B cells, called autoantibodies. These AAgs are divided into two categories on the basis of beta-cell-specificity. The list of the targets associated with beta cell-specific AAgs is continuously growing. Many T1DM-associated AAgs are well characterized and have important clinical applications for disease prediction, diagnosis, and antigen-specific tolerance immunotherapy. Identification of T1DM-associated AAgs provides insight into the pathogenesis of T1DM and to understanding the clinical aspects of the disease. Since many excellent reviews have covered the previously identified T1DM-associated AAgs exhaustedly, here we only focus on several recently discovered T1DM-AAgs (PDX1, ZnT8, CHGA, and IAAP).
    American Journal of Translational Research 05/2013; 5(4):379-92. · 3.40 Impact Factor
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    ABSTRACT: The large worldwide variation in type 1 diabetes incidence and increasing incidence over time points toward important environmental risk factors. Among them, nutrition plays an important role. The objective was to investigate the relationship between type 1 diabetes and nutritional factors in pregnancy and early in life. We carried out, using semi-quantitative food frequency questionnaires, a retrospective case-control study in 298 children of 0-15 years old, 145 of which were affected by type 1 diabetes. The diet of all children and of their mothers during pregnancy and lactation was assessed. In children, a statistically significant dose-response association between type 1 diabetes and the amount of meat consumption was found while no other nutritional factors were associated with the disease. High meat consumption seems to be an important early in life cofactor for type 1 diabetes development, although these findings need to be confirmed in wider prospective follow-up studies.
    Acta Diabetologica 03/2012; 50(5). DOI:10.1007/s00592-012-0385-2 · 2.40 Impact Factor
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    ABSTRACT: Type 1 diabetes (T1D) is an autoimmune disease characterized by known genetic risk factors with T cell-mediated infiltration and destruction of the beta cells within pancreatic islets. Autoantibodies are the most significant preclinical marker of T1D, and birth cohort studies have provided important insights into the natural history of autoimmunity and T1D. While HLA remains the strongest genetic risk factor, a number of novel gene variants associated with T1D have been found through genome-wide studies, some of which have been linked to suspected environmental risk factors. Multiple environmental factors that have been suggested to play a role in the development of T1D await confirmation. Current risk-stratification models for T1D take into account genetic risk factors and autoantibodies. In the future, metabolic profiles, epigenetics, as well as environmental risk factors may be included in such models.
    Annals of the New York Academy of Sciences 01/2013; 1281(1). DOI:10.1111/nyas.12021 · 4.38 Impact Factor
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