Enflurane and adenosine 3',5'-cyclic monophosphate metabolism in pancreatic islets

The effects of enflurane at a concentration of 4% by volume in the gas phase upon rates of insulin secretion were correlated with islet contents of adenosine 3',5'-cyclic monophosphate (cyclic AMP). At this concentration, enflurane was without effect upon the basal rate of insulin release in the presence of 2 mM glucose. By contrast, the anesthetic led to 84 and 86% inhibitions, respectively, of rates of insulin secretion stimulated by 20 mM glucose and 20 mM glucose plus 1 mM theophylline. Enflurane also led to small reductions in islet cyclic AMP content under all conditions of incubation, and a statistically significant (P less than 0.02) effect of the anesthetic in lowering cyclic AMP content was seen in islets exposed to 20 mM glucose plus 1 mM theophylline. Enflurane was without effect upon the activity of the low Km cyclic AMP phosphodiesterase of the islet under the conditions employed. By contrast, the anesthetic led to significant inhibitions of both basal and fluoride-stimulated islet adenylate cyclase activity (34%, P less than 0.01 and 23%, P less than 0.005, respectively). It is concluded that under the conditions employed, enflurane leads to inhibition of islet adenylate cyclase activity and to small resultant reductions in islet cyclic AMP content. These effects appear to be of insufficient magnitude to explain completely the observed degree of insulin secretory inhibition by the anesthetic.