Effects of forskolin on insulin release and cyclic AMP content in rat pancreatic islets

The effects of forskolin, a diterpene stimulator of adenylate cyclase, on cyclic AMP content and insulin release, have been studied in rat pancreatic islets. In the presence of 2.8 mM glucose, 0.3 to 30 microM forskolin gave concentration-dependent increases in cyclic AMP content to as much as seven-fold without causing any significant increase in insulin release. With 5.6 mM glucose, cyclic AMP contents were elevated by forskolin to the same extent as with 2.8 mM glucose but, under these conditions, insulin release was stimulated. 3 microM forskolin was a maximal concentration with respect to insulin release, but not for the elevation of cyclic AMP levels. Concentration-dependent increases in both insulin release and cyclic AMP content were detected over the range of 0.3 to 3 microM forskolin. The effect of forskolin to stimulate insulin release was rapid and was reversible within 15 minutes of removal of the drug. When tested with 16.7 mM glucose, forskolin potentiated both phases of stimulated release, with the greater effect upon the first phase.