Complement-fixing Islet cell antibodies from some diabetic patients alter insulin release in vitro.
To explore humoral immunity in insulin-dependent diabetic (IDDM) patients, we studied insulin release from isolated mouse islets stimulated by glucose + theophylline after incubation with the sera of these patients and complement. Eleven of 21 IDDM sera suppressed the stimulated insulin release while the arginine-stimulated glucagon release remained unchanged. Morphologic evidence and the trypan-blue exclusion test suggested that the suppression of insulin release was due to a cytotoxic effect of the sera. No beta-cell inhibition of morphologic damage was detectable in the presence of sera from 30 healthy subjects, 8 non-insulin-dependent diabetic patients, and 5 nondiabetic patients with autoimmune diseases. Beta-cell inhibition by IDDM sera was not observed when complement was omitted. After serum fractionation, the cytotoxic potency of IDDM sera was located in the immunoglobulin G fraction. Using human islets, insulin release was suppressed by 3 of 6 IDDM sera. Complement-dependent cytotoxicity was found in 1 of 5 recent-onset IDDM patients and 11 of 16 IDDM patients with autoimmune phenomena. It was associated in all cases with the presence of islet cell antibodies as detected by immunofluorescence, and with the presence of circulating lymphocytes which suppressed insulin release in vitro. Complement-fixing antibodies may contribute to the selective beta-cell damage in IDDM.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000917:Antibody Formation; D001120:Arginine; D001681:Biological Assay; D002648:Child; D003168:Complement Fixation Tests; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged
D007328:Insulin; D005934:Glucagon; D001120:Arginine