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 - Endocrinology and Metabolism
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:
https://lup.lub.lu.se/record/1113496
- author
- Salehi, S Albert
LU
; Mosén, Henrik
LU
and Lundquist, Ingmar
LU
- organization
- publishing date
- 1998
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- carbachol, emiglitate, calcium ion, nifedipine, pancreatic islets, lysosomal enzymes
- in
- American Journal of Physiology - Endocrinology and Metabolism
- volume
- 274
- issue
- 3
- pages
- 459 - 468
- publisher
- American Physiological Society
- external identifiers
-
- pmid:9530129
- ISSN
- 1522-1555
- 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
- 2016-04-01 15:23:47
- date last changed
- 2020-09-16 15:24:57
@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 = {{1522-1555}},
keywords = {{carbachol; emiglitate; calcium ion; nifedipine; pancreatic islets; lysosomal enzymes}},
language = {{eng}},
number = {{3}},
pages = {{459--468}},
publisher = {{American Physiological Society}},
series = {{American Journal of Physiology - Endocrinology and Metabolism}},
title = {{Insulin release transduction mechanism through acid glucan 1,4-alpha-glucosidase activation is Ca2+ regulated}},
url = {{http://ajpendo.physiology.org/cgi/content/full/274/3/E459}},
volume = {{274}},
year = {{1998}},
}