DUAL EFFECT OF FORMYCIN A UPON THE HYDROLYSIS OF PHOSPHOINOSITIDES INPERIFUSED PANCREATIC-ISLETS

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