Major Histocompatibility Complex Molecules and the Beta Cell: Inferences from Transgenic Models
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Type 1 or insulin-dependent diabetes mellitus is a syndrome of chronic hyperglycaemia secondary to insulin deficiency due to the selective destruction of the pancreatic islet β cells. The molecular pathology of the disease in humans is still poorly understood, but a substantial body of evidence favours the view that the β cells are destroyed by an autoimmune process initiated in genetically predisposed individuals by environmental agents such as viruses or chemotoxins (EISENBARTH 1986; ROSSINI et al. 1988; CAMPBELL and HARRISON 1989). Evidence in humans for the autoimmune basis of type 1 diabetes includes the following: (a) the presence of circulating autoantibodies to islet cells and/or insulin in the majority of newly diagnosed patients (GLEICHMANN and BOTTAZZO 1987), (b) mononuclear cell infiltration or “insulitis” of islets seen in the pancreas obtained at autopsy from newly diagnosed subjects (GEPTS and LE COMPTE 1981; FOULIS et al. 1986), (c) recurrence of diabetes associated with insulitis in recipients of pancreas isografts from major histocompatibility complex (MHC) identical siblings (SIBLEY et al. 1985) and (d) an increase in the frequency and duration of remissions from insulin dependence in newly diagnosed patients treated with immunosuppressive agents (HARRISON et al. 1985; ASSAN et al. 1985).
KeywordsBeta Cell Major Histocompatibility Complex Class Major Histocompatibility Complex Molecule Major Histocompatibility Complex Protein Human Islet Cell
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