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Insulin release transduction mechanism through acid glucan 1,4-alpha-glucosidase activation is Ca2+ regulated

Salehi, S Albert LU ; Mosén, Henrik LU and Lundquist, Ingmar LU (1998) In American Journal of Physiology 274(3). p.459-468
Abstract
An important signal involved in glucose-stimulated insulin secretion is transduced through the action of a lysosomal acid, glucan 1,4-alpha-glucosidase. We investigated the Ca2+ dependency of this enzyme activity in relation to insulin release. In isolated islets, increased levels of extracellular Ca2+ induced a large increase in acid glucan 1,4-alpha-glucosidase activity accompanied by a similar increase in insulin release at both substimulatory and stimulatory concentrations of glucose. At low glucose the Ca2+ "inflow" blocker nifedipine unexpectedly stimulated enzyme activity without affecting insulin release. However, nifedipine suppressed 45Ca2+ outflow from perifused islets at low glucose and at Ca2+ deficiency when intracellular... (More)
An important signal involved in glucose-stimulated insulin secretion is transduced through the action of a lysosomal acid, glucan 1,4-alpha-glucosidase. We investigated the Ca2+ dependency of this enzyme activity in relation to insulin release. In isolated islets, increased levels of extracellular Ca2+ induced a large increase in acid glucan 1,4-alpha-glucosidase activity accompanied by a similar increase in insulin release at both substimulatory and stimulatory concentrations of glucose. At low glucose the Ca2+ "inflow" blocker nifedipine unexpectedly stimulated enzyme activity without affecting insulin release. However, nifedipine suppressed 45Ca2+ outflow from perifused islets at low glucose and at Ca2+ deficiency when intracellular Ca2+ was mobilized by carbachol. This nifedipine-induced retention of Ca2+ was reflected in increased acid glucan 1,4-alpha-glucosidase activity. Adding different physiological Ca2+ concentrations or nifedipine to islet homogenates did not increase enzyme activity. Neither selective glucan 1,4-alpha-glucosidase inhibition nor the ensuing suppression of glucose-induced insulin release was overcome by a maximal Ca2+ concentration. Hence, Ca(2+)-induced changes in acid glucan 1,4-alpha-glucosidase activity were intimately coupled to similar changes in Ca(2+)-glucose-induced insulin release. Ca2+ did not affect the enzyme itself but presumably activated either glucan 1,4-alpha-glucosidase-containing organelles or closely interconnected messengers. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
carbachol, emiglitate, calcium ion, nifedipine, pancreatic islets, lysosomal enzymes
in
American Journal of Physiology
volume
274
issue
3
pages
459 - 468
publisher
American Pysiological Society
external identifiers
  • pmid:9530129
ISSN
0002-9513
language
English
LU publication?
yes
id
68dc3632-5eb1-4df4-ab24-57e8f6c55533 (old id 1113496)
alternative location
http://ajpendo.physiology.org/cgi/content/full/274/3/E459
date added to LUP
2008-07-15 11:01:11
date last changed
2016-04-16 02:54:49
@article{68dc3632-5eb1-4df4-ab24-57e8f6c55533,
  abstract     = {An important signal involved in glucose-stimulated insulin secretion is transduced through the action of a lysosomal acid, glucan 1,4-alpha-glucosidase. We investigated the Ca2+ dependency of this enzyme activity in relation to insulin release. In isolated islets, increased levels of extracellular Ca2+ induced a large increase in acid glucan 1,4-alpha-glucosidase activity accompanied by a similar increase in insulin release at both substimulatory and stimulatory concentrations of glucose. At low glucose the Ca2+ "inflow" blocker nifedipine unexpectedly stimulated enzyme activity without affecting insulin release. However, nifedipine suppressed 45Ca2+ outflow from perifused islets at low glucose and at Ca2+ deficiency when intracellular Ca2+ was mobilized by carbachol. This nifedipine-induced retention of Ca2+ was reflected in increased acid glucan 1,4-alpha-glucosidase activity. Adding different physiological Ca2+ concentrations or nifedipine to islet homogenates did not increase enzyme activity. Neither selective glucan 1,4-alpha-glucosidase inhibition nor the ensuing suppression of glucose-induced insulin release was overcome by a maximal Ca2+ concentration. Hence, Ca(2+)-induced changes in acid glucan 1,4-alpha-glucosidase activity were intimately coupled to similar changes in Ca(2+)-glucose-induced insulin release. Ca2+ did not affect the enzyme itself but presumably activated either glucan 1,4-alpha-glucosidase-containing organelles or closely interconnected messengers.},
  author       = {Salehi, S Albert and Mosén, Henrik and Lundquist, Ingmar},
  issn         = {0002-9513},
  keyword      = {carbachol,emiglitate,calcium ion,nifedipine,pancreatic islets,lysosomal enzymes},
  language     = {eng},
  number       = {3},
  pages        = {459--468},
  publisher    = {American Pysiological Society},
  series       = {American Journal of Physiology},
  title        = {Insulin release transduction mechanism through acid glucan 1,4-alpha-glucosidase activation is Ca2+ regulated},
  volume       = {274},
  year         = {1998},
}