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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1021590
- author
- Speidel, Dina
LU
; Salehi, S Albert
LU
; Obermueller, Stefanie
; Lundquist, Ingmar
LU
; Brose, Nils
; Renström, Erik
LU
and Rorsman, Patrik
LU
- organization
- publishing date
- 2008
- 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
- pmid:18177725
- 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
- 2016-04-04 08:56:43
- date last changed
- 2022-01-29 07:55:54
@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}},
doi = {{10.1016/j.cmet.2007.11.009}},
volume = {{7}},
year = {{2008}},
}