The effects of sera obtained from children with insulin-dependent diabetes mellitus on cultivated islet cells: cytotoxicity and insulin release.

Abstract

Sera were obtained from 24 patients with newly-diagnosed insulin-dependent diabetes mellitus (IDDM) and 14 children with a high risk of diabetes. The influence of the decomplementated sera on basal and stimulated insulin secretion was studied in a mixed culture of newborn rat islet cells. In addition, complement-dependent antibody-mediated cytotoxicity (C'AMC) was measured by 51Cr-release from pre-labelled islet cells. Incubation of the islet cells with sera from ten IDDM patients did not affect the basal insulin release. Sera from other children with IDDM (n = 14) either significantly increased (n = 7) or inhibited (n = 7) basal IRI secretion was compared with the sera of control donors. Nearly half of the sera from the high-risk children was found to be insulin-stimulating. Preincubation of islet cells with sera from IDDM children caused a significant decrease of insulin response to 16.5 mM glucose plus 5 mM theophylline (P less than 0.001). Sera from the high-risk children did influence the response of pancreatic cells to secretagogues. C'AMC was found in 45% of the patients with IDDM and in 33% of the high-risk children, however, there was no correlation between C'AMC and serum effect upon basal insulin secretion. These results suggest the presence of B-cytotropic factors in serum from children with IDDM or with a risk of diabetes. Opposite effects of different sera on insulin secretion may reflect the variety of pathogenetic mechanisms involved in islet cell destruction.