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CAPS1 and CAPS2 Regulate Stability and Recruitment of Insulin Granules in Mouse Pancreatic beta Cells.

Speidel, Dina LU ; Salehi, S Albert LU ; Obermueller, Stefanie; Lundquist, Ingmar LU ; Brose, Nils; Renström, Erik LU and Rorsman, Patrik LU (2008) In Cell Metabolism 7(1). p.57-67
Abstract
CAPS1 and CAPS2 regulate dense-core vesicle release of transmitters and hormones in neuroendocrine cells, but their precise roles in the secretory process remain enigmatic. Here we show that CAPS2(-/-) and CAPS1(+/-);CAPS2(-/-) mice, despite having increased insulin sensitivity, are glucose intolerant and that this effect is attributable to a marked reduction of glucose-induced insulin secretion. This correlates with diminished Ca(2+)-dependent exocytosis, a reduction in the size of the morphologically docked pool, a decrease in the readily releasable pool of secretory vesicles, slowed granule priming, and suppression of second-phase (but not first-phase) insulin secretion. In beta cells of CAPS1(+/-);CAPS2(-/-) mice, the lowered insulin... (More)
CAPS1 and CAPS2 regulate dense-core vesicle release of transmitters and hormones in neuroendocrine cells, but their precise roles in the secretory process remain enigmatic. Here we show that CAPS2(-/-) and CAPS1(+/-);CAPS2(-/-) mice, despite having increased insulin sensitivity, are glucose intolerant and that this effect is attributable to a marked reduction of glucose-induced insulin secretion. This correlates with diminished Ca(2+)-dependent exocytosis, a reduction in the size of the morphologically docked pool, a decrease in the readily releasable pool of secretory vesicles, slowed granule priming, and suppression of second-phase (but not first-phase) insulin secretion. In beta cells of CAPS1(+/-);CAPS2(-/-) mice, the lowered insulin content and granule numbers were associated with an increase in lysosome numbers and lysosomal enzyme activity. We conclude that although CAPS proteins are not required for Ca(2+)-dependent exocytosis to proceed, they exert a modulatory effect on insulin granule priming, exocytosis, and stability. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Metabolism
volume
7
issue
1
pages
57 - 67
publisher
Cell Press
external identifiers
  • pmid:18177725
  • wos:000252235100009
  • scopus:37449005991
ISSN
1550-4131
DOI
10.1016/j.cmet.2007.11.009
language
English
LU publication?
yes
id
a5f6101b-eba2-4ec6-abc3-4834011bbfc8 (old id 1021590)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18177725?dopt=Abstract
date added to LUP
2008-02-13 15:15:37
date last changed
2017-10-22 04:56:21
@article{a5f6101b-eba2-4ec6-abc3-4834011bbfc8,
  abstract     = {CAPS1 and CAPS2 regulate dense-core vesicle release of transmitters and hormones in neuroendocrine cells, but their precise roles in the secretory process remain enigmatic. Here we show that CAPS2(-/-) and CAPS1(+/-);CAPS2(-/-) mice, despite having increased insulin sensitivity, are glucose intolerant and that this effect is attributable to a marked reduction of glucose-induced insulin secretion. This correlates with diminished Ca(2+)-dependent exocytosis, a reduction in the size of the morphologically docked pool, a decrease in the readily releasable pool of secretory vesicles, slowed granule priming, and suppression of second-phase (but not first-phase) insulin secretion. In beta cells of CAPS1(+/-);CAPS2(-/-) mice, the lowered insulin content and granule numbers were associated with an increase in lysosome numbers and lysosomal enzyme activity. We conclude that although CAPS proteins are not required for Ca(2+)-dependent exocytosis to proceed, they exert a modulatory effect on insulin granule priming, exocytosis, and stability.},
  author       = {Speidel, Dina and Salehi, S Albert and Obermueller, Stefanie and Lundquist, Ingmar and Brose, Nils and Renström, Erik and Rorsman, Patrik},
  issn         = {1550-4131},
  language     = {eng},
  number       = {1},
  pages        = {57--67},
  publisher    = {Cell Press},
  series       = {Cell Metabolism},
  title        = {CAPS1 and CAPS2 Regulate Stability and Recruitment of Insulin Granules in Mouse Pancreatic beta Cells.},
  url          = {http://dx.doi.org/10.1016/j.cmet.2007.11.009},
  volume       = {7},
  year         = {2008},
}