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Cited by 75Pancreatic function and diabetesCellular transport and secretionCalcium signaling and nucleotide metabolism

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

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Speidel, Dina, Salehi, Albert, Obermueller, Stefanie, Lundquist, Ingmar, Brose, Nils, Renström, Erik, Rorsman, Patrik·2008·Cell Metabolism
DOI 10.1016/j.cmet.2007.11.009
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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.

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  • CAPS proteins are not required for insulin secretion and depolarization-evoked exocytosis proceeds even in their complete absence.

    “CAPS proteins are not required for insulin secretion and depolarization-evoked exocytosis proceeds even in their complete absence (i.e. in Cadps and Cadps2 double knockout mice) (638).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [638]

    The Results report depolarization-evoked exocytosis in embryonic CAPS1/CAPS2 double-knockout β cells, and the Discussion concludes that CAPS proteins are not required for exocytosis. Insulin secretion was measured only in mice with CAPS2 absent and CAPS1 present or partially present; it was reduced but persisted. The paper therefore does not establish that insulin secretion proceeds in the complete absence of both proteins. (LLM, conf=0.86)

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  • CAPS proteins affect granule stability and their ablation leads to increased crinophagy.

    “For example, CAPS proteins affect granule stability and their ablation leads to increased crinophagy (638).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [638]

  • In Cadps2 knockout mice, 1st phase insulin secretion is unaffected but 2nd phase secretion is strongly reduced.

    “In Cadps2 knockout mice, 1st phase insulin secretion is unaffected but 2nd phase secretion is strongly reduced, consistent with the idea that the protein plays a role in granule priming (638).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [638]

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Research works printed but not linked: 27

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Cited by

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Authors
Speidel, D., Salehi, A., Obermueller, S., Lundquist, I., Brose, N., Renström, E., & Rorsman, P.
Affiliations
  • Lund University (SE)
  • Max Planck Institute of Experimental Medicine (DE)
  • Churchill Hospital (GB)
Corresponding author
Speidel, Dina
ORCID
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2008-01
Volume
7
Issue
1
Pages
57-67
ISSN
1550-4131 (ISSN-L)
DOI
10.1016/j.cmet.2007.11.009
OpenAlex
W2038771045
Cited by
75
References
5
Citations by year
2025: 3 · 2024: 2 · 2023: 3 · 2021: 8 · 2020: 2 · 2019: 5 · 2018: 5 · 2017: 5 · 2016: 5 · 2015: 6 · 2014: 4 · 2013: 6 · 2012: 3
FWCI
6.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
  • GRO (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
  • Vetenskapsrådet
  • Wellcome Trust
  • Deutsche Forschungsgemeinschaft
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
insulin granules, pancreatic beta cells, insulin secretion, impaired glucose tolerance, insulin sensitivity, exocytosis, granule stability, lysosomes, lysosomal enzyme activity, second-phase insulin secretion, first-phase insulin secretion, dense core vesicles
MeSH terms
Animals, Calcium, Calcium-Binding Proteins, Electrophysiology, Exocytosis, Immunohistochemistry, Insulin, Islets of Langerhans, Lysosomes, Nerve Tissue Proteins, Mice, Knockout, Microscopy, Confocal, Pancrelipase, Microscopy, Electron, Transmission, Insulin-Secreting Cells, Mice

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