Insulin and type 1 diabetes: immune connections.
Insulin is the hormone produced by pancreatic β-cells, with a central role in carbohydrate and fat metabolism. Together with its precursors preproinsulin and proinsulin, insulin is also a key target antigen (Ag) of the autoimmune islet destruction leading to type 1 diabetes. Being recognized by both autoantibodies (aAbs) and autoreactive T cells, insulin plays a triggering role, at least in rodent models, in diabetes pathogenesis. It is expressed not only by β-cells but also in the thymus, where it plays a major role in central tolerance mechanisms. We will summarize current knowledge concerning insulin, its role in β-cell autoimmunity as initial target Ag, its recognition by aAbs and autoreactive T cells, and the detection of these immune responses to provide biomarkers for clinical trials employing insulin as an immune modulatory agent.
INSERM, U986, DeAR Lab Avenir, Saint Vincent de Paul Hospital, 82 Avenue Denfert Rochereau, 75674 Paris Cedex 14, France.
Sloboda
S
Culina
Vedran
V
Brezar
Roberto
R
Mallone
D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism; D010179:Pancreas / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D001323:Autoantibodies; D007328:Insulin