Non-selective inhibition of insulin and glucagon release by xenogeneic islet cell surface antibodies

Abstract

The influence of xenogeneic islet cell surface antibodies (ICSA) on the hormonal secretion of non-B islet cells has not been completely elucidated. Accordingly, we investigated the influence of xenogeneic antiserum on glucagon release from A cells, as representative of non-B islet cells, together with other characteristics of the antiserum. Anti-islet cell sera were produced in rabbits by xenogeneic immunization with dispersed hamster islet cells. Rabbit anti-hamster islet cell surface antibodies were detected both qualitatively by indirect immunofluorescence analyses and quantitatively by 125I-protein A radioligand assay. However, antiserum did not induce cell surface immunofluorescence on rat or mouse islet cells. As a result of evaluation of the specific cytotoxicity using 51Cr release assay, antiserum was observed to induce a significantly higher release of 51Cr compared with that of normal rabbit serum in complement-dependent antibody-mediated cytotoxicity. Both glucose-stimulated insulin and arginine-stimulated glucagon release were suppressed by xenogeneic antiserum not only in the presence but also in the absence of complement. It is concluded, therefore, that xenogeneic antiserum has a relative species specificity and non-selectively binds to islet cells in contrast with the non-species specificity and preferential binding to pancreatic B cells of human ICSA, although heterogeneity in ICSA-positive sera has been suggested.