EFFECTS OF ISLET CELL-SURFACE ANTIBODIES AND COMPLEMENT ON THE RELEASE OF INSULIN AND CHROMIUM FROM PERIFUSED BETA-CELLS

Abstract

The dynamics of insulin and Cr release from prelabeled rat pancreatic islet cells were studied by perifusion of cells supported in a column of Bio-Gel P-2 polyacrylamide beads. The column-perifused .beta. cells released insulin in a biphasic pattern in response to 30 mmol/l D-glucose and in a monophasic pattern to 20 mmol/l L-arginine. Rat islet cells, 1st exposed to a rabbit anti-rat islet cell surface serum and complement and then added to the column, were unable to release insulin in response to 30 mmol/l D-glucose and 0.1 mmol/l 3-isobutyl-1-methylxanthine. To study cytotoxicity by an additional approach, islet cells were prelabeled with radioactive chromium (Na251CrO4). These cells did not release either insulin or 51Cr in response to glucose. Exposure of the cells to surface antiserum and complement before perifusion did not induce either Cr or insulin release. Similar results were obtained when glucose alone or combined with surface antiserum was added to the perifusate bathing rat islet cells incubated with 0.1 mmol/l non-radioactive Na2CrO4 before perifusion. A transient, dramatic release of insulin from these cells was induced by adding complement to the perifusion medium (containing surface antibodies). Complement-dependent cytotoxicity of islet cell surface antibodies apparently involves different phenomena. The cytotoxic reaction results in a transient release of insulin whether the physiological release mechanisms were blocked by Cr or not. In cells not treated with Cr the cytotoxic reactions renders the .beta. cells unable to release insulin in response to glucose.