Islet beta-cytotoxic monoclonal antibody against glycolipids in experimental diabetes induced by low dose streptozotocin and Freund's adjuvant |
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Authors: | M Ziegler S Teneberg S Witt B Ziegler B Hehmke K D Kohnert J Egeberg K A Karlsson A Lernmark |
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Institution: | Hagedorn Research Laboratory, Gentofte, Denmark. |
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Abstract: | Diabetes was induced in BALB/c mice by four injections of a subdiabetogenic dose (40 mg/kg) of streptozotocin in combination with CFA. The treatment increased the plasma glucose from 5.8 +/- 0.1 to 22.1 +/- 1.3 mmol/liter (n = 9). The diabetic animals had circulating islet cell surface antibodies (75%), and a monoclonal islet cell surface IgM antibody, K56aF3, generated from one of the diabetic BALB/c mice, mediated C-Dependent cytotoxicity against insulin-producing cells and inhibited glucose-stimulated insulin release from isolated rat islets. Solid phase assay on thin layer chromatograms showed no binding of the K56aF3 antibody to glycolipids prepared from relevant cells. However, testing against a series of glycolipids of various non-pancreatic origins showed a preferential binding to a nine-sugar glycolipid isolated from human erythrocytes carrying an unusual blood group A determinant (type 3). It is suggested that this mAb may be associated with the development of diabetes following a combination of polyclonal activation and non-diabetogenic doses of streptozotocin. |
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