Effect of prolonged administration of cyclosporin A on (pro)insulin biosynthesis and insulin release by rat islets of Langerhans.

One group of rats received, an oral dose of 25 mg/kg body weight of Cyclosporin A daily for 21 consecutive days in olive oil, whereas the control group received an equal amount of the vehicle for the same period. On the 22nd day animals selected at random from both the groups were subjected to glucose tolerance (1.5 g/kg body weight/oral). The blood sugar values indicated glucose intolerance in experimental rats compared to vehicle-treated rats. The remaining animals were killed, and the pancreases were separated for islet isolation. After incubation of islets for 3 hr at 37 degrees with different glucose challenges, a highly significant (P less than 0.001) lowering of (pro)insulin biosynthesis, significant decrease in IRI release as well as significant inhibition in activities of acid phosphatase and cathepsin B was seen.