Effect of chloroquine on biosynthesis, release and degradation of insulin in isolated islets of rat pancreas.

Insulin has been reported to degrade inside the islets and islet lysosomal proteases have been thought to take part. As chloroquine is regarded as a potent lysosomotropic agent, an attempt has been made to see whether chloroquine has an influence on intrainsular degradation of insulin. After preculture of collagenase-isolated rat islets at 11 mM glucose together with [3H]leucine for 3 days for labelling newly synthesized insulin, islets were cultured for 1 day at 2.2 or 22 mM glucose with or without 0.02 mM chloroquine. Afterwards, radioactivity was measured in the proinsulin/insulin fraction. For control, the influence of chloroquine during 3-h incubation of both freshly isolated and precultured islets was also studied. During the 1-day culture at 2.2 mM glucose, prelabelled insulin was degraded significantly and addition of chloroquine did not alter the amount of insulin degraded. At 22 mM glucose, no significant amount of insulin had been degraded. During the 3-h incubation of freshly isolated as well as precultured islets, chloroquine was found to inhibit significantly glucose-induced biosynthesis of insulin. Glucose-induced release of insulin, however, was not influenced by chloroquine. It is concluded that chloroquine does not influence glucose-induced release or intra-insular degradation of insulin, but it interferes with the biosynthesis of insulin.