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

Lebrun, Philippe; Renström, Erik LU ; Antoine, Marie-Hélène; Bokvist, Krister; Holmquist, Mats; Rorsman, Patrik and Malaisse, W J (1996) In Pflügers Archiv 431(3). p.353-362
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Insulin release, Pancreatic islet, Formycin A
in
Pflügers Archiv
volume
431
issue
3
pages
353 - 362
publisher
Springer
external identifiers
  • pmid:8584428
  • scopus:0029688128
ISSN
0031-6768
language
English
LU publication?
yes
id
1752a91d-7fa9-4808-b989-678bc8fe8b2f (old id 1109891)
date added to LUP
2008-07-25 14:43:26
date last changed
2017-01-01 06:48:21
@article{1752a91d-7fa9-4808-b989-678bc8fe8b2f,
  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.},
  author       = {Lebrun, Philippe and Renström, Erik and Antoine, Marie-Hélène and Bokvist, Krister and Holmquist, Mats and Rorsman, Patrik and Malaisse, W J},
  issn         = {0031-6768},
  keyword      = {Insulin release,Pancreatic islet,Formycin A},
  language     = {eng},
  number       = {3},
  pages        = {353--362},
  publisher    = {Springer},
  series       = {Pflügers Archiv},
  title        = {Dynamics of the cationic, bioelectrical and secretory responses to formycin A in pancreatic islet cells},
  volume       = {431},
  year         = {1996},
}