Inhibition of insulin release after passive transfer of immunoglobulin from insulin-dependent diabetic children to mice.

We used the mouse passive transfer model to test whether islet cell antibodies affect beta-cell function. The immunoglobulin (Ig) fraction of plasma from 5 islet cell surface antibody-positive, newly diagnosed insulin-dependent diabetic children or of a pool of plasma from 12 normal subjects was injected daily (7-16 mg IgG/day) for 14 days into normal immunosuppressed BALB/c mice. Insulin secretory responses in the Ig-injected mice were then examined by perfusing the rodent pancreata in vitro. Insulin release induced by 20 mmol/liter D-glucose during 30 min of stimulation decreased from 900 ng insulin (median; range, 814-1138) from pancreata of mice injected with control Ig to 511 ng (range, 130-786) from pancreata of mice injected with diabetic Ig (P less than 0.003). Both the initial peak and the sustained second phase of glucose-stimulated insulin release were depressed in 4 of the 5 pancreata from mice injected with diabetic Ig. These results indicate that circulating antibodies in diabetic children may alter beta-cell function and possibly contribute to the pathogenesis of insulin-dependent diabetes.