Dual effect of formycin a upon the hydrolysis of phosphoinositides in perifused pancreatic islets

Formycin A (1.0 mM) caused a rapid, sustained and rapidly reversible inhibition of effluent radioactivity in rat pancreatic islets prelabelled with myo-2-³H]inositol and perifused in the presence of 8.3 mM -glucose. This coincided with a progressive decrease in islet ATP content and transient inhibition of insulin release. Theraafter, however, formycin A increased glucose-induced insulin release. Moreover, in islets that were preincubated with myo-2-³H]inositol and then exposed during perifusion to a rise in -glucose concentration from 2.8 to 16.7 mM, the release of insulin and ³H fractional outflow rate at both the low and high hexose concentrations were much higher when both the preincubation and perifusion were conducted in the presence, rather than absence, of formycin A. It is concluded that formycin A first inhibits and later enhances both the hydrolysis of phosphoinositides and release of insulin, these effects being possibly related to changes in the islet cell content of adenosine and/or formycin A triphosphates.