Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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)
Please use this url to cite or link to this publication:
author
; ; ; ; ; and
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
2016-04-01 15:50:43
date last changed
2022-01-28 07:27:53
@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}},
  keywords     = {{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}},
}