Beyond the hormone: insulin as an autoimmune target in type 1 diabetes.
Endocr Rev
; 32(5): 623-69, 2011 Oct.
Article
em En
| MEDLINE
| ID: mdl-21700723
ABSTRACT
Insulin is not only the hormone produced by pancreatic ß-cells but also a key target antigen of the autoimmune islet destruction leading to type 1 diabetes. Despite cultural biases between the fields of endocrinology and immunology, these two facets should not be regarded separately, but rather harmonized in a unifying picture of diabetes pathogenesis. There is increasing evidence suggesting that metabolic factors (ß-cell dysfunction, insulin resistance) and immunological components (inflammation and ß-cell-directed adaptive immune responses) may synergize toward islet destruction, with insulin standing at the crossroad of these pathways. This concept further calls for a revision of the classical dichotomy between type 1 and type 2 diabetes because metabolic and immune mechanisms may both contribute to different extents to the development of different forms of diabetes. After providing a background on the mechanisms of ß-cell autoimmunity, we will explain the role of insulin and its precursors as target antigens expressed not only by ß-cells but also in the thymus. Available knowledge on the autoimmune antibody and T-cell responses against insulin will be summarized. A unifying scheme will be proposed to show how different aspects of insulin biology may lead to ß-cell destruction and may be therapeutically exploited. We will argue about possible reasons why insulin remains the mainstay of metabolic control in type 1 diabetes but has so far failed to prevent or halt ß-cell autoimmunity as an immune modulatory reagent.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autoantígenos
/
Autoimunidade
/
Diabetes Mellitus Tipo 1
/
Insulina
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article