Effects of chloroquine on lipid metabolism of mouse pancreatic islets

Pancreatic islets accumulate the amphiphilic drug, chloroquine, which leads to a marked impairment of the insulin production of the B-cells in vitro. In this study the effects of the drug on islet lipid metabolism in vitro were investigated. It was found that exposure of islets to chloroquine (10(-5) M) for one week induced an increase of D-[U-14C]glucose incorporation into phospholipids and triacylglycerols of about two-fold and into diacylglycerols of about six-fold. Furthermore, two-dimensional thin-layer chromatography showed an increased rate of D-[U-14C]glucose incorporation into all major phospholipid classes. A 17% increase of the total islet phospholipid content indicated that an accumulation of islet cell phospholipids occurred. Pulse-chase experiments with D-[U-14C]glucose showed that the rate of degradation of islet phospholipids was decreased after prolonged exposure to chloroquine. No short-term effects of chloroquine upon either the de novo biosynthesis of islet lipids or upon phospholipid degradation could be demonstrated. The present data therefore suggest that chloroquine impairs the rate of islet lipid degradation in long-term experiments, which may be a primary lesion in the sequence of events leading to functional impairment of the B-cell.