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Glucose-dependent docking and SNARE protein-mediated exocytosis in mouse pancreatic alpha-cell.

Andersson, Sofia; Pedersen, Morten Gram LU ; Vikman, Jenny LU and Eliasson, Lena LU (2011) In Pflugers Archiv : European journal of physiology 462(3). p.443-454
Abstract
The function of alpha-cells in patients with type 2 diabetes is often disturbed; glucagon secretion is increased at hyperglycaemia, yet fails to respond to hypoglycaemia. A crucial mechanism behind the fine-tuned release of glucagon relies in the exocytotic machinery including SNARE proteins. Here, we aimed to investigate the temporal role of syntaxin 1A and SNAP-25 in mouse alpha-cell exocytosis. First, we used confocal imaging to investigate glucose dependency in the localisation of SNAP-25 and syntaxin 1A. SNAP-25 was mainly distributed in the plasma membrane at 2.8 mM glucose, whereas the syntaxin 1A distribution in the plasma membrane, as compared to the cytosolic fraction, was highest at 8.3 mM glucose. Furthermore, following... (More)
The function of alpha-cells in patients with type 2 diabetes is often disturbed; glucagon secretion is increased at hyperglycaemia, yet fails to respond to hypoglycaemia. A crucial mechanism behind the fine-tuned release of glucagon relies in the exocytotic machinery including SNARE proteins. Here, we aimed to investigate the temporal role of syntaxin 1A and SNAP-25 in mouse alpha-cell exocytosis. First, we used confocal imaging to investigate glucose dependency in the localisation of SNAP-25 and syntaxin 1A. SNAP-25 was mainly distributed in the plasma membrane at 2.8 mM glucose, whereas the syntaxin 1A distribution in the plasma membrane, as compared to the cytosolic fraction, was highest at 8.3 mM glucose. Furthermore, following inclusion of an antibody against SNAP-25 or syntaxin 1A, exocytosis evoked by a train of ten depolarisations and measured as an increase in membrane capacitance was reduced by ~50%. Closer inspection revealed a reduction in the refilling of granules from the reserve pool (RP), but also showed a decreased size of the readily releasable pool (RRP) by ~45%. Disparate from the situation in pancreatic beta-cells, the voltage-dependent Ca(2+) current was not reduced, but the Ca(2+) sensitivity of exocytosis decreased by the antibody against syntaxin 1A. Finally, ultrastructural analysis revealed that the number of docked granules was >2-fold higher at 16.7 mM than at 1 mM glucose. We conclude that syntaxin 1A and SNAP-25 are necessary for alpha-cell exocytosis and regulate fusion of granules belonging to both the RRP and RP without affecting the Ca(2+) current. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pflugers Archiv : European journal of physiology
volume
462
issue
3
pages
443 - 454
publisher
Springer
external identifiers
  • wos:000293954700007
  • pmid:21643653
  • scopus:80052511774
ISSN
1432-2013
DOI
10.1007/s00424-011-0979-5
language
English
LU publication?
yes
id
b95c8232-5332-467d-b4fc-e590c08e26d9 (old id 2008474)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21643653?dopt=Abstract
date added to LUP
2011-07-03 19:24:39
date last changed
2017-03-26 04:02:07
@article{b95c8232-5332-467d-b4fc-e590c08e26d9,
  abstract     = {The function of alpha-cells in patients with type 2 diabetes is often disturbed; glucagon secretion is increased at hyperglycaemia, yet fails to respond to hypoglycaemia. A crucial mechanism behind the fine-tuned release of glucagon relies in the exocytotic machinery including SNARE proteins. Here, we aimed to investigate the temporal role of syntaxin 1A and SNAP-25 in mouse alpha-cell exocytosis. First, we used confocal imaging to investigate glucose dependency in the localisation of SNAP-25 and syntaxin 1A. SNAP-25 was mainly distributed in the plasma membrane at 2.8 mM glucose, whereas the syntaxin 1A distribution in the plasma membrane, as compared to the cytosolic fraction, was highest at 8.3 mM glucose. Furthermore, following inclusion of an antibody against SNAP-25 or syntaxin 1A, exocytosis evoked by a train of ten depolarisations and measured as an increase in membrane capacitance was reduced by ~50%. Closer inspection revealed a reduction in the refilling of granules from the reserve pool (RP), but also showed a decreased size of the readily releasable pool (RRP) by ~45%. Disparate from the situation in pancreatic beta-cells, the voltage-dependent Ca(2+) current was not reduced, but the Ca(2+) sensitivity of exocytosis decreased by the antibody against syntaxin 1A. Finally, ultrastructural analysis revealed that the number of docked granules was >2-fold higher at 16.7 mM than at 1 mM glucose. We conclude that syntaxin 1A and SNAP-25 are necessary for alpha-cell exocytosis and regulate fusion of granules belonging to both the RRP and RP without affecting the Ca(2+) current.},
  author       = {Andersson, Sofia and Pedersen, Morten Gram and Vikman, Jenny and Eliasson, Lena},
  issn         = {1432-2013},
  language     = {eng},
  number       = {3},
  pages        = {443--454},
  publisher    = {Springer},
  series       = {Pflugers Archiv : European journal of physiology},
  title        = {Glucose-dependent docking and SNARE protein-mediated exocytosis in mouse pancreatic alpha-cell.},
  url          = {http://dx.doi.org/10.1007/s00424-011-0979-5},
  volume       = {462},
  year         = {2011},
}