MODULATION OF BETA-CELL ACTIVITY AND ITS INFLUENCE ON ISLET-CELL ANTIBODY (ICA) AND ISLET-CELL SURFACE ANTIBODY (ICSA) REACTIVITY

Insulin-dependent diabetes mellitus (IDDM) is associated with the form ation of autoantibodies against different antigens in the islets of La ngerhans, so-called islet cell antibodies (ICA). The expression of a m ajor autoantigen, the beta-cell specific enzyme glutamic acid decarbox ylase (GAD), is glucose-dependent in vitro and correlated to insulin r elease in vitro. In this study the expression of islet autoantigens wa s examined in vivo and the relationship between beta-cell function and islet cell surface antibody (ICSA) reactivity was tested. Rats were f ed for 10 days with glipizide or diazoxide, in order to stimulate or i nhibit insulin release, respectively. Frozen sections of pancreata wer e incubated with ten ICA-positive IDDM sera and analyzed by indirect i mmunofluorescence. Two sera with a ''beta-cell restricted'' staining, five with an ''all-islet cell'' staining and three with a ''mixed'' pa ttern were employed. In all three groups, the highest end-point titres were obtained when pancreata of rats treated with glipizide were used . Intermediate titres were seen in control animals and the lowest titr es were observed on pancreata from diazoxide-treated rats, regardless of the serum used. In contrast to these observations, no correlation b etween ICSA reactivity and islet cell activity could be demonstrated. Conflicting results concerning ICSA in previous reports and our failur e to show a glucose regulation of ICSA reactivity, indicate that ICSA is a phenomenon with a low degree of specificity. The observation that the recognition of islet cells by autoantibodies is influenced by the metabolic state of the islets in vivo suggests that the level of auto antigen expression could be of importance in determining the intensity of the autoimmune destructive process present at the onset of IDDM.