Effects of streptozotocin in vitro on proinsulin biosynthesis,insulin release and ATP content of isolated rat islets of Langerhans

Summary Proinsulin synthesis, insulin release and intracellular ATP concentrations were measured in isolated rat islets of Langerhans under control conditions of in vitro incubation and after treatment with several concentrations of streptozotocin for different periods of time. It was found that streptozotocin inhibited proinsulin synthesis, as well as insulin release, in a time and concentration dependent manner. The characteristics of the inhibition of these two processes were similar in general terms, but one dissimilarity was noted, i.e. after 60 min exposure to a high concentration of streptozotocin, proinsulin synthesis was inhibited more than insulin release. ATP content was reduced by high concentrations of streptozotocin, but it was found that proinsulin synthesis and insulin release could be inhibited without any effect on ATP content by a low (0.22 mM) concentration of streptozotocin. The effect of streptozotocin on proinsulin synthesis was judged to be the result of a target specificity for the B-cell rather than a specific effect on proinsulin relative to total protein synthesis.This work was supported by the Swiss National Scientific Foundation (Grant No. 3106073), Berne, Switzerland, and by a grant-in-aid from Hoechst Pharmaceuticals, Frankfurt-Hoechst, GermanyPreliminary data from this work were presented at the European Symposium on Hypoglycemia, Rome, April 5–6, 1974