Diethyldithiocarbamate, but not disulfiram, inhibits alloxan-induced dye accumulation of isolated mouse islet beta-cells.

Abstract

The diabetogenic action of alloxan on pancreatic beta-cells is thought to be mediated by hydroxyl radicals. The initial attack of the radicals is probably at the plasma membrane level. Diethyldithiocarbamate (DDTC) and its dimer disulfiram (Antabuse) have recently been shown to protect against damage by free radical generating agents. The ability of DDTC and disulfiram to inhibit alloxan-induced dye accumulation of isolated ob/ob mice islet beta-cells was therefore studied. Evans blue was used as an indicator of plasma membrane permeability. DDTC (100 microM 1 mM) but not disulfiram (100 microM 1 mM) inhibited alloxan-induced dye uptake of beta-cells. The effect of DDTC on oxygen consumption in a mixture of reduced glutathione (GSH), alloxan and FeSO4 was studied with a Clark-type oxygen electrode. DDTC (20, 100 microM) had no effect on the oxygen consumption of this mixture. It is suggested that the DDTC inhibition of alloxan-induced dye uptake of isolated beta-cells takes place at a step beyond the generation of free radicals.