Stimulation of insulin and glucagon synthesis in rat Langerhans islets by malathion in vitro: Evidence for mitochondrial interaction and involvement of subcellular non-cholinergic mechanisms

Abstract: We examined the effects of malathion, an organophosphorus (OP) insecticide, on glucagon, C-peptide, and insulin content or secretion from isolated rat Langerhans islets in vitro. Islets were isolated from the pancreas of rats by standard collagenase digestion, separation by centrifugation, and hand-picking technique. Then islets were cultured in medium and supplemented with various concentrations of malathion (25, 125, and 625μg/ml) for 1, 3, and 5h. In vitro exposure to malathion increased insulin and C-peptide contents at doses of 25, 125, and 625μg/ml following 5h incubation as compared to control. All doses of malathion increased glucagon content after 3 and 5h as compared to control. Increase of the glucagon content at all doses in the fifth hour was higher than that of third hour. Malathion also decreased 2.8 and 16.7mM glucose-stimulated insulin secretion at all doses after 30min as compared to control. It is concluded that malathion reduce insulin exocytose in a short time (first hour) but after a long time (e.g., 5h), the content of insulin is increased by compensating mechanisms such as resynthesize of insulin or aggregation of insulin. The present in vitro study for the first time proposes the involvement of subcellular non-cholinergic mechanisms in malathion-induced changes in Langerhans islets insulin and glucagon. [Copyright &y& Elsevier]