The Effect of Chloroquine on the Binding, Intracellular Distribution, and Action of Insulin on Isolated Mouse Pancreatic Acini

Abstract

The effects of chloroquine on the binding, intracellular distribution, and action of insulin were studied in isolated pancreatic acini prepared from diabetic mice. Chloroquine had three effects on these cells. First, chloroquine altered cellular morphology by inducing an increase in the number and size of autophagic vacuoles and vesicles in the Golgi-lysosomal region. Second, chloroquine, in a dose-dependent fashion, increased the amount of 125I-insulin associated with acini. A detectable effect of chloroquine was seen at 10 microM, and a maximal effect was seen at 30-100 microM where cell-associated insulin was more than doubled. Employing electron microscope autoradiographs, this accumulation of hormone was observed in the Golgi-lysosome area of the pancreatic acinar cell. Third, chloroquine had selective effects on the action of insulin. Preincubation with chloroquine had no effect on basal [3H]2-deoxy-D-glucose uptake, but in a dose-dependent fashion it decreased the stimulatory effect of insulin on this function; at 100 microM chloroquine, the effect of insulin was abolished. In contrast, chloroquine had negligible effects on the stimulation of 2-deoxy-D-glucose uptake into acini by cholecystokinin. Chloroquine in dose-dependent fashion partially inhibited basal [3H]leucine incorporation into acinar cell protein, but in contrast to its effects on 2-deoxy-D-glucose uptake, the drug had no effects on the stimulation of this function by insulin.+2