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

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.