A quantitative method for circulating islet cell surface antibodies (ICSA), based on the binding of125I-protein A to insulin-producing RINm5F cells, was used to evaluate ICSA in plasma of 4- to 40-week-old Aston obese hyperglycaemic (ob/ob) mice and normal control (+/+) mice. RINm5F cells bound 2502 ± l196 c.p.m.125I-protein A per 105 cells (mean ± S.D., n = 54) after incubation with +/+ plasma. ICSA positive plasma (defined as125I-protein A binding, mean ± 2 S.D. of +/+ plasma) was detected in 3 out of 54+/+ mice and 3 out of 54 ob/ob mice. ICSA were not observed in ob/ob mice before the onset of diabetes (7 weeks of age), but were detected at 9, 20 and 40 weeks. At 20 weeks125I-protein A binding produced by ob/ob plasma was 35% greater than +/+ plasma (P < 0.05). The low occurrence of ICSA in ob/ob mice (6%) suggests that factors other than ICSA are responsible for B-cell dysfunction and eventual islet degeneration observed in Aston ob/ob mice.

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