Possible role of diadenosine polyphosphates in glucose-stimulated insulin release: Effects of NaF upon metabolic and functional variables in rat isolated islets

Diadenosine polyphosphates, such as diadenosine triphosphate (A2P3) and dia denosine tetraphosphate (A2P4), were recently proposed to participate in th e stimulus-secretion coupling for nutrient-stimulated insulin release. Sinc e NaF, an inhibitor of inorganic pyrophosphatase, was reported to lower A2P 3 and A2P4 content in glucose-stimulated pancreatic islets, its effects upo n metabolic, cationic, biosynthetic and secretory variables in rat pancreat ic islets were investigated in the present study. Up to a concentration clo se to 0.1 mM, NaF failed to affect most of these variables, except for a de crease in Ca-45 net uptake. Much higher concentrations of NaF (e.g. 5.0 mM) were required to cause inhibition of the metabolic, ionic, biosynthetic an d secretory responses of the islets to nutrient secretagogues. Yet, even at this high concentration, NaF failed to lower the islet content in tritiate d A2P3 and A2P4 in islets prelabelled with [2,8-H-3]adenosine and failed to prevent the glucose-induced increase in such a content. It is concluded, t herefore, that NaF may not represent a suitable tool to assess the particip ation of diadenosine polyphosphates in the process of nutrient-induced insu lin secretion.