Diadenosine Polyphosphates: A Novel Class of Glucose-Induced Intracellular Messengers in the Pancreatic β-Cell

Diadenosine polyphosphates are a group of low-weight compounds that increase after exposure to a wide variety of oxidants and have been suggested to act as “alarmones,” alerting the cell to the onset of metabolic stress. We demonstrate here that glucose at concentrations that induce insulin release produce a 30- to 70-fold increase in the concentration of diadenosine triphosphate (Ap₃A) and tetraphosphate (Ap₄A) in β-cells. Furthermore, Ap₃A and Ap₄A, at the concentrations found in glucose-stimulated cells, are effective inhibitors of the ATP-regulated K+ channels when applied to the intracellular side of excised membrane patches from cultured β-cells. We suggest that Ap₃A and Ap₄A act as second messengers mediating a glucose-induced blockade of the pancreatic β-cell ATP-regulated potassium channel.