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Inhibition of Insulin Release after Passive Transfer of Immunoglobulin from Insulin-Dependent Diabetic Children to Mice^*

ANNETTE SVENNINGSEN, THOMAS DYRBERG, IVAN GERLING, ÅKE LERNMARK, PETER MACKAY and ALEXANDER RABINOVITCH

Hagedorn Research Laboratory, DK-2820 Gentofte Denmark

Address all correspondence and requests for reprints to: Åke Lernmark, M.D., Director of Research, Hagedorn Research Laboratory, Niels Steensensvej 6, DK-2820 Gentofte, Denmark.

We used the mouse passive transfer model to test whether islet cell antibodies affect β-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 Dglucose 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 < 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 β-cell function and possibly contribute to the pathogenesis of insulin-dependent diabetes.

^* This work was supported in part by NIH Grant AM-26190.

Supported by a fellowship from the University of Copenhagen Medical Faculty.

Supported by NIH Research Career Development Award 5K04-AM-00552.

Received April 20, 1983.