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Title of Journal: Pflugers Arch

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Abbravation: Pflügers Archiv - European Journal of Physiology

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Springer Berlin Heidelberg

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DOI

10.1007/bf03004688

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1432-2013

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Inosine partially mimics the effects of glucose on

Authors: M Bozem M G Garrino J C Henquin
Publish Date: 1987/11/01
Volume: 410, Issue: 4-5, Pages: 457-463
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Abstract

The purine ribonucleoside inosine is known to be metabolized in islet cells its ribose moiety feeds into the pentosephosphate cycle and stimulate insulin release but the mechanisms of this stimulation have not been established These were investigated with mouse islets In the absence of glucose 5 mM inosine decreased86Rb+ efflux from islet cells depolarized the Bcell membrane induced electrical activity slow waves of membrane potential with bursts of spikes on the plateau accelarated45Ca2+ efflux and stimulated insulin release with the same efficiency as 10 mM glucose Raising the concentration of inosine to 20 mM only had a slight further effect and in particular failed to cause persistent depolarization of the Bcell membrane The electrical activity triggered by inosine was blocked by cobalt and the stimulation of45Ca2+ efflux and insulin release was abolished in a Ca2+free medium The effects of 10 mM glucose on electrical activity45Ca2+ efflux and insulin release were augmented by as little as 05 mM inosine All effects of inosine were abolished by an inhibitor of nucleoside transport nitrobenzylthioguanosine and markedly impaired by inhibitors of nucleoside phosphorylase formycin B or of glycolysis iodoacetate In conclusion inosine metabolism in Bcells induces insulin release by triggering the same sequence of events as glucose metabolism a decrease of K+ permeability of the Bcell membrane leading to depolarization and activation of voltagedependent Ca channels

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