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

På svenska

Author

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

Summary, in English

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.

Publishing year

1996

Language

English

Pages

353-362

Publication/Series

Pflügers Archiv

Volume

431

Issue

3

Document type

Journal article

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Keywords

  • Insulin release
  • Pancreatic islet
  • Formycin A

Status

Published

Research group

  • Diabetes - Islet Patophysiology

ISBN/ISSN/Other

  • ISSN: 0031-6768