Abstract
A number of beta cell antigens have been identified as important targets for the pancreatic islet directed autoimmunity underlying insulin dependent diabetes (IDD), through their reactivities to autoantibodies or peripheral blood T cells in patients prior to and/or at diagnosis. Three of the more important appear to be the 65KDa isoform of glutamic acid decarboxylase (GAD65) a 38KDa beta cell specific protein of undetermined origin and insulin. In non-obese diabetic (NOD) mice, prophylactic daily, subcutaneously insulin therapy both prevents diabetes and attentuates the degree of insulitis seen. The mechanism may involve ‘beta cell nest’ and possibly tolerance induced by insulin immunization. These data have led to the initiation of a randomized human trial in non-diabetic relatives with a positive islet cell antibody (ICA) of >720 JDF who also have impaired first phase insulin release (FPIR) to IV glucose. Diabetes in NOD mice can also be delayed by the introduction of oral feedings of porcine insulin or human GADK presumably through a mechanism of tolerance induction, and human trials are planned among relatives with strongly positive ICA but normal FPIR. Immunization of NOD mice with insulin in incomplete Freunds adjuvant also specifically delays diabetes, an effect not seen by immunization with BSA, the BSA (ABBOS) peptide, nor human insulin A chain. These findings indicate progress towards the prevention of IDD and provide the rationale for the institution of clinical trials.
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Maclaren, N., Schatz, D., Song, Y. et al. ANTIGEN DIRECTED THERAPIES TO PREVENT INSULIN DEPENDENT DIABETES. Pediatr Res 33 (Suppl 5), S4 (1993). https://doi.org/10.1203/00006450-199305001-00014
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DOI: https://doi.org/10.1203/00006450-199305001-00014
