Removal of Ca2+ Channel β3 Subunit Enhances Ca2+ Oscillation Frequency and Insulin Exocytosis
Open accessAbstract
An oscillatory increase in pancreatic beta cell cytoplasmic free Ca2+ concentration, [Ca2+]i, is a key feature in glucose-induced insulin release. The role of the voltage-gated Ca2+ channel beta3 subunit in the molecular regulation of these [Ca2+]i oscillations has now been clarified by using beta3 subunit-deficient beta cells. beta3 knockout mice showed a more efficient glucose homeostasis compared to wild-type mice due to increased glucose-stimulated insulin secretion. This resulted from an increased glucose-induced [Ca2+]i oscillation frequency in beta cells lacking the beta3 subunit, an effect accounted for by enhanced formation of inositol 1,4,5-trisphosphate (InsP3) and increased Ca2+ mobilization from intracellular stores. Hence, the beta3 subunit negatively modulated InsP3-induced Ca2+ release, which is not paralleled by any effect on the voltage-gated L type Ca2+ channel. Since the increase in insulin release was manifested only at high glucose concentrations, blocking the beta3 subunit in the beta cell may constitute the basis for a novel diabetes therapy.
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Granule mobility is very low in the absence of ATP, but increases with a rise in the intracellular ATP concentration.
“Granule mobility is very low in the absence of ATP, but increases with a rise in the intracellular ATP concentration (57, 702).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [57]
The Results and Discussion passage describes glucose-induced Ca2+ oscillations, while the exocytosis passage describes responses to depolarization; neither addresses granule mobility. Searches for granule mobility, ATP dependence, and intracellular ATP concentration found only an account of extracellular ATP promoting Ca2+ release (section labeled Abstract; page unavailable), not the claimed relationship. (LLM, conf=0.74)
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Cites
Structure and Regulation of Voltage-Gated Ca <sup>2+</sup> Channels
Catterall, W. A. (2000) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.16.1.521 · Cited by 2,344 · see citing works
Biden, T. J., Peter-Riesch, B., Schlegel, W., & Wollheim, C. B. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)61389-4 · Cited by 157 · see citing works
Ämmälä, C., Larsson, O., Berggren, P., Bokvist, K. B., Juntti‐Berggren, L., Kindmark, H., & Rorsman, P. (1991) · Nature · doi:10.1038/353849a0 · Cited by 128 · see citing works
Self-citationCa2+ and pancreatic B-cell function
Berggren, P., & Larsson, O. (1994) · Biochemical Society Transactions · doi:10.1042/bst0220012 · Cited by 83 · see citing works
Self-citationPhosphorylated inositol compounds in β-cell stimulus-response coupling
Barker, C. J., Leibiger, I. B., Leibiger, B., & Berggren, P. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00088.2002 · Cited by 46 · see citing works
Self-citationBarker, C. J., French, P. J., Moore, A. J., Nilsson, T., Berggren, P., Bunce, C. M., Kirk, C. J., & Michell, R. H. (1995) · Biochemical Journal · doi:10.1042/bj3060557 · Cited by 41 · see citing works
Self-citationBarker, C. J., Nilsson, T., Kirk, C. J., et al. (1994) · Biochemical Journal · doi:10.1042/bj2970265 · Cited by 16 · see citing works
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- [2]2. Arikkath, J. ∙ Campbell, K.P. Auxiliary subunitsessential components of the voltage-gated calcium channel complex Curr. Opin. Neurobiol. 2003; 13:298-307 Crossref Scopus (437) PubMed Google Scholar
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Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793 · see citing works
Short Telomeres Compromise β-Cell Signaling and Survival
Guo, N., Parry, E. M., Li, L.-S., Kembou, F., Lauder, N., Hussain, M. A., Berggren, P.-O., & Armanios, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017858 · Cited by 100 · see citing works
Self-citationPhospholipase C‐β1 potentiates glucose‐stimulated insulin secretion
Hwang, H.-J., Yang, Y. R., Kim, H. Y., Choi, Y., Park, K.-S., Lee, H., Ma, J. S., Yamamoto, M., Kim, J., Chae, Y. C., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201802732rr · Cited by 20 · see citing works
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- Authors
- Berggren, P.-O., Yang, S.-N., Murakami, M., Efanov, A. M., Uhles, S., Köhler, M., Moede, T., Fernström, A., Appelskog, I. B., Aspinwall, C. A., Zaitsev, S. V., Larsson, O., de Vargas, L. M., Fecher-Trost, C., Weißgerber, P., Ludwig, A., Leibiger, B., Juntti-Berggren, L., Barker, C. J., Gromada, J., Freichel, M., Leibiger, I. B., & Flockerzi, V.
- Affiliations
- Karolinska University Hospital (SE)
- Saarland University (DE)
- Technical University of Munich (DE)
- Corresponding author
- Berggren, Per-Olof
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2004-10
- Volume
- 119
- Issue
- 2
- Pages
- 273-284
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1998269481
- Cited by
- 114
- References
- 7
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 3 · 2022: 7 · 2021: 2 · 2020: 1 · 2019: 6 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 4 · 2014: 13 · 2013: 4 · 2012: 3
- FWCI
- 7.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3211 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 58508, R01DK058508)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- insulin exocytosis, pancreatic beta cells, glucose-stimulated insulin secretion, inositol 1,4,5-trisphosphate, IP3 receptor, glucose homeostasis, diabetes treatment
- MeSH terms
- Animals, Calcium, Cells, Cultured, Enzyme Inhibitors, Exocytosis, Glucose, Homeostasis, Insulin, Islets of Langerhans, Calcium Channels, Inositol 1,4,5-Trisphosphate, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Patch-Clamp Techniques, Thapsigargin, COS Cells, Calcium Signaling, Protein Subunits, Mice, Inositol 1,4,5-Trisphosphate Receptors
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