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Inosine partially mimics the effects of glucose on ionic fluxes, electrical activity, and insulin release in mouse pancreatic B-cells

  • M. Bozem
  • M. -G. Garrino
  • J. -C. Henquin
Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands

Abstract

The purine ribonucleoside inosine is known to be metabolized in islet cells (its ribose moiety feeds into the pentose-phosphate 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 B-cell 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 B-cell 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 activity,45Ca2+ efflux and insulin release were augmented by as little as 0.5 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 B-cells induces insulin release by triggering the same sequence of events as glucose metabolism: a decrease of K+ permeability of the B-cell membrane, leading to depolarization and activation of voltage-dependent Ca channels.

Key words

Inosine Insulin release Ionic fluxes Pancreatic islets B-cell membrane potential 

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Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • M. Bozem
    • 1
  • M. -G. Garrino
    • 2
  • J. -C. Henquin
    • 1
    • 2
  1. 1.I. Physiologisches InstitutUniversität des SaarlandesHomburg/SaarFederal Republic of Germany
  2. 2.Unité de Diabétologie et Nutrition, Faculty of MedicineUniversité de LouvainBrusselsBelgium

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