Chronic chloroquine treatment enhances insulin release in rats

The effects of chronic chloroquine treatment on intravenous glucose tolerance, and the plasma insulin response to intravenous glucose were studied in rats. Plasma glucose disappearance constants (Kg) were significantly greater (6.2 +/- 0.5% min-1) than in corresponding controls (3.7 +/- 0.4% min-1, p less than 0.001). This improved glucose tolerance was associated with significantly higher plasma immunoreactive insulin levels in response to glucose injection. Islets isolated from rats treated with chloroquine showed significantly enhanced (P less than 0.05) insulin release when incubated with 16.7 mM glucose but not with lower glucose concentrations (3 and 8 mM). Pre-incubation of islets with streptozotocin (0.05-1.5 mg/ml) produced a dose-dependent reduction in glucose-stimulated insulin secretion which was not modified in islets from chloroquine-treated rats. The concentration of chloroquine in the pancreas increased rapidly during administration and reached a value of 20.2 +/- 0.7 micrograms/g (fresh weight) after 20 weeks of treatment. It is concluded that chronic chloroquine treatment results in an improved glucose tolerance associated with an enhanced glucose-induced insulin secretion. Although earlier work showed chloroquine to reduce the severity of diabetes induced subsequently with streptozotocin, the present study shows that such an amelioration was not due to a protective effect against the beta-cell cytotoxic action of streptozotocin.