Beta Cell Destruction in Type 1 Diabetes

Presentation Note on Mechanism of Beta Cell & what causes beta cell destruction in type 1 diabetes for Medical & Biology Students in word / .doc Format

Mechanisms of b - Cell Destruction :

Although the clinical onset of type 1 diabetes is abrupt, this disease  infact results form a chronic autoimmune attack on cells that usually starts many years before the disease becomes evident. The classic manifestations of the disease (hyperglycemia and ketosis) occur late in its course, after more than 90% of the b - cells have been destroyed. Several mechanisms contribute to b cell destruction.

T lymphocytes react against b - cells antigens and cause damage. These T cells include (1) CD4+ T cells of the TH1 subset, which cause tissue injury by activating macrophages, and (2) CD8+ cytotoxic T lymphocytes, which directly kill cells and also secrete cytokines that activate macrophages. In the rare cases in which the pancreatic lesions have been examined at the early active stages of the disease, the islets show cellular necrosis and lymphocytic infiltration. This lesion is called insulitis. The infiltrates consists of both CD4+, and CD8+ T cells. Surviving b - cells often express class II MHC molecules, probably an effect of local production of the cytokine IFN- g by the T cells. The specificity of these T – cells is largely unknown. Various studies have implicated a b cell enzyme, glutamic acid decarboxylase (GAD), and insulin itself as autoantigens, but the evidence supporting their importance is mainly circumstantial.

Locally produced cytokines damage b cells. Among the cytokines implicated in the cell injury are IFN- g produced by T cells, and IL-1, produced by macrophages that are activated during the immune reaction. All these cytokines have been shown to induce b- cell apoptosis in culture .In mouse models of the disease, b- cell destruction can be reduced by treatment with antagonists against these cytokines.

Autoantibodies against islet cells and insulin are also detected in the blood of 70% to 80% of patients. The autoantibiodies are reactive with a variety of b cell antigens, including GAD. These antibodies participate in causing the disease or may be a result of T cell mediated cell injury and release of normally sequestered antigens.

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