Dynamics of the cationic, bioelectrical and secretory responses to formycin A in pancreatic islet cells
(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:
https://lup.lub.lu.se/record/1109891
- author
- Lebrun, Philippe ; Renström, Erik LU ; Antoine, Marie-Hélène ; Bokvist, Krister ; Holmquist, Mats ; Rorsman, Patrik and Malaisse, W J
- organization
- publishing date
- 1996
- 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}},
}