Diabetes, Vol 45, Issue 10 1431-1434, Copyright © 1996 by American Diabetes Association

ARTICLES

Diadenosine polyphosphates. A novel class of glucose-induced intracellular messengers in the pancreatic beta-cell

C Ripoll, F Martin, J Manuel Rovira, J Pintor, MT Miras-Portugal and B Soria
Department of Physiology, University of Alicante, School of Medicine, Spain.

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 beta-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 beta-cells. We suggest that Ap3A and Ap4A act as second messengers mediating a glucose-induced blockade of the pancreatic beta-cell ATP-regulated potassium channel.
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