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 formation of autoantibodies against different antigens in the islets of Langerhans, so-called islet cell antibodies (ICA). The expression of a major autoantigen, the beta-cell specific enzyme glutamic acid decarboxylase (GAD), is glucose-dependent in vitro and correlated to insulin release in vitro. In this study the expression of islet autoantigens was examined in vivo and the relationship between beta-cell function and islet cell surface antibody (ICSA) reactivity was tested. Rats were fed for 10 days with glipizide or diazoxide, in order to stimulate or inhibit insulin release, respectively. Frozen sections of pancreata were incubated with ten ICA-positive IDDM sera and analyzed by indirect immunofluorescence. Two sera with a "beta-cell restricted" staining, five with an "all-islet cell" staining and three with a "mixed" pattern 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 titres were observed on pancreata from diazoxide-treated rats, regardless of the serum used. In contrast to these observations, no correlation between ICSA reactivity and islet cell activity could be demonstrated. Conflicting results concerning ICSA in previous reports and our failure to show a glucose regulation of ICSA reactivity, indicate that ICSA is a phenomenon with a low degree of specificity.(ABSTRACT TRUNCATED AT 250 WORDS)
Björk
E
E
Department of Internal Medicine, University Hospital, Uppsala University, Sweden.
Kämpe
O
O
Grawé
J
J
Hallberg
A
A
Norheim
I
I
Karlsson
F A
FA
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D003981:Diazoxide / Q000494:pharmacology; D005434:Flow Cytometry; D005913:Glipizide / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D001323:Autoantibodies; C024211:islet cell antibody; D003981:Diazoxide; D005913:Glipizide