Evidence for complement-dependent and -independent inhibition of insulin secretion from clonal beta-cells incubated in the presence of sera of newly diagnosed IDDM patients

There are conflicting reports on the effect of serum from patients with ins ulin-dependent diabetes mellitus (IDDM) or normal human serum on beta-cell function and insulin secretion. Here, we report that the sera of newly diag nosed IDDM patients potently suppresses insulin secretion from a clonal rat pancreatic beta-cell line (BRIN-BD11), but do not alter cell viability. In deed, the viability of the beta-cells was not significantly different betwe en cells cultured in 10% (v/v) IDDM sera, normal human sera, or fetal calf serum after 24, 48 and 72 h. Alanine-stimulated insulin secretion from cell s cultured for 24 h in (10% v/v) IDDM patient sera was reduced to 48% of th at secreted from cells cultured in (10% v/v) normal human sera. After deple tion of the complement components C1q and C3, the inhibition of insulin sec retion induced by IDDM patient sera was significantly reversed (no signific ant difference was observed between cells cultured in complement-depleted I DDM patient sera and cells cultured in normal human sera or complement-depl eted normal human sera). The concentration of glutamic acid decarboxylase (GAD) autoantibodies was m arkedly increased in the sera of six out of nine newly diagnosed IDDM patie nts in this study, whereas insulin auto-antibodies (IAA) were detected in t he sera of three of the nine patients and islet-cell antibodies (ICA) in th e sera of five of them. In addition, the concentration of soluble terminal complement complexes (SC5b-9) was greater in some of the beta-cell culture media samples after 24 h incubation when the incubation medium was suppleme nted with IDDM patient sera than when supplementation was with normal human sera. We propose that the mechanism of sera-induced inhibition of insulin secreti on from clonal beta-cells may involve complement- and cytokine-stimulated i ntracellular events that attenuate the metabolite-induced secretory process .