Dynamics of the cationic, bioelectrical and secretory responses to formycin A in pancreatic islet cells

Philippe Lebrun, Erik Renström, Marie-Hélène Antoine, Krister Bokvist, Mats Holmquist, Patrik Rorsman, W J Malaisse

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5 Citations (SciVal)

Abstract

The dynamics of the cationic, bioelectrical and secretory responses to formycin A were monitored in pancreatic islet cells in order to assess whether this adenosine analogue, which is known to be converted to formycin A 5'-triphosphate in isolated islets, triggers the same sequence of ionic events as that otherwise involved in the process of nutrient-stimulated insulin release and currently attributed to an increase in adenosine 5'-triphosphate (ATP) generation rate. Unexpectedly, formycin A first increased 86Rb outflow, decreased 45Ca outflow and inhibited insulin release from prelabelled islets perifused at physiological or higher concentrations of D-glucose. This early inhibitory effect of formycin A upon insulin release coincided, in perforated patch whole-cell recordings, with an initial transient increase of ATP-sensitive K+ channel activity. A positive secretory response to formycin A, still not associated with any decrease in K+ conductance, was only observed either immediately after formycin A administration to islets already exposed to glibenclamide or during prolonged exposure to the adenosine analogue. This coincided with an increase of cytosolic Ca2+ concentration in intact B-cells and a greater increase of membrane capacitance in response to depolarization in B-cells examined in the perforated patch whole-cell configuration. The latter stimulation of exocytotic activity could not be attributed, however, to any increase in peak or integrated Ca2+ current. Thus, the mode of action of formycin A, or its 5'-triphosphate ester, in islet cells obviously differs from that currently ascribed to endogenous ATP in the process of nutrient-stimulated insulin release.
Original languageEnglish
Pages (from-to)353-362
JournalPflügers Archiv
Volume431
Issue number3
Publication statusPublished - 1996

Subject classification (UKÄ)

  • Endocrinology and Diabetes

Keywords

  • Insulin release
  • Pancreatic islet
  • Formycin A

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