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 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.
Ripoll
C
C
Department of Physiology, University of Alicante, School of Medicine, Spain.
Martin
F
F
Manuel Rovira
J
J
Pintor
J
J
Miras-Portugal
M T
MT
Soria
B
B
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D015290:Second Messenger Systems / Q000187:drug effects* / Q000502:physiology
D015226:Dinucleoside Phosphates; D015221:Potassium Channels; C020733:diadenosine tetraphosphate; C011440:diadenosine triphosphate; D000255:Adenosine Triphosphate; D005947:Glucose