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.
D000293:Adolescent; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001323:Autoantibodies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007116:Immunization, Passive; D007136:Immunoglobulins / Q000276:immunology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism
D000906:Antibodies; D001323:Autoantibodies; D007136:Immunoglobulins; D007328:Insulin; C024211:islet cell antibody; D005947:Glucose