DIADENOSINE POLYPHOSPHATES - A NOVEL CLASS OF GLUCOSE-INDUCED INTRACELLULAR MESSENGERS IN THE PANCREATIC BETA-CELL

Diadenosine polyphosphates are a group of low-weight compounds that in crease after exposure to a wide variety of oxidants and have been sugg ested to act as ''alarmones,'' alerting the cell to the onset of metab olic stress. We demonstrate here that glucose at concentrations that i nduce insulin release produce a 30- to 70-fold increase in the concent ration of diadenosine triphosphate (Ap(3)A) and tetraphosphate (Ap(4)A ) in beta-cens. Furthermore, Ap(3)A and Ap(4)A, at the concentrations found in glucose-stimulated cells, are effective inhibitors of the ATP -regulated K+ channels when applied to the intracellular side of excis ed membrane patches from cultured beta-cens. We suggest that Ap(3)A an d Ap(4)A act as second messengers mediating a glucose-induced blockade of the pancreatic beta-cell ATP-regulated potassium channel.