抄録
Type 1 diabetes of both the human and NOD mouse is associated with autoimmunity directed against insulin which is the only β cell specific autoantigen. Variable number of tandem repeats in the 5′ region of insulin gene on chromosome 11 is associated with the risk of type 1 diabetes in human. Mice have two insulin genes including the insulin 1 gene (chromsome 19) and the insulin 2 gene (chromsome 7). The insulin 2 gene knockout when bred onto NOD mice accelerates diabetes. In contrast to insulin 2, diabetes and insulitis were markedly reduced in insulin 1 knockout mice with decreased and delayed diabetes. Autoantibodies to insulin can predict diabetes in man and NOD mice. Insulin peptides can be used to induce insulitis and diabetes in non-diabetic strain mice. Our results suggest that insulin molecule is a possible “primary” autoantigen that initiates a pathogenesis of type 1 diabetes. An administration of insulin or its peptide can prevent the development of diabetes in NOD mice but we cannot at present safely prevent type 1 diabetes in humans. A series of clinical trials are under way and planned.
