Impaired insulin secretion and glucose tolerance in β cell‐selective CaV1.2 Ca2+ channel null mice
Open accessAbstract
Insulin is secreted from pancreatic beta cells in response to an elevation of cytoplasmic Ca(2+) resulting from enhanced Ca(2+) influx through voltage-gated Ca(2+) channels. Mouse beta cells express several types of Ca(2+) channel (L-, R- and possibly P/Q-type). beta cell-selective ablation of the gene encoding the L-type Ca(2+) channel subtype Ca(v)1.2 (betaCa(v)1.2(-/-) mouse) decreased the whole-cell Ca(2+) current by only approximately 45%, but almost abolished first-phase insulin secretion and resulted in systemic glucose intolerance. These effects did not correlate with any major effects on intracellular Ca(2+) handling and glucose-induced electrical activity. However, high-resolution capacitance measurements of exocytosis in single beta cells revealed that the loss of first-phase insulin secretion in the betaCa(v)1.2(-/-) mouse was associated with the disappearance of a rapid component of exocytosis reflecting fusion of secretory granules physically attached to the Ca(v)1.2 channel. Thus, the conduit of Ca(2+) entry determines the ability of the cation to elicit secretion.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Mouse β-cells express L-type Ca2+ channels (Cacna1c and Cacna1d) and smaller amounts of N- and P/Q-type Ca2+ channels.
“Mouse β-cells express L-type Ca2+ channels (Cacna1c and Cacna1d) and smaller amounts of N- (Cacna1b) and P/Q-type (Cacna1a) Ca2+ channels (211, 222, 603) (seem Appendix Figure 3A).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [603]
In “Mouse L-type Ca²⁺ channel variety expressed in β cells is Caᵥ1.2” (page unavailable), the paper says Caᵥ1.2 is the only L-type variety expressed in mouse β-cells, contrary to the claim that they also express Caᵥ1.3 (Cacna1d). It identifies the other channel types as R and P/Q, rather than N and P/Q. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredA cocktail of isradipine, SNX482, ω-contoxin and ω-agatoxin almost completely inhibits the β-cell whole-cell Ca2+ current.
“A cocktail of isradipine, SNX482, ω-contoxin and ω-agatoxin almost completely inhibits the β-cell whole-cell Ca2+ current (603).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [603]
The Results report that isradipine reduced β-cell Ca2+ current by 53 ± 6%, and the Figure 2 caption describes adding SNX482 after isradipine. Our copy does not report testing ω-conotoxin or ω-agatoxin in that combination, or show that a four-drug cocktail almost completely inhibited the whole-cell current. (LLM, conf=0.85)
Experimental — accuracy not yet measuredCacna1c (Cav1.2) is particularly important for 1st phase insulin secretion, possibly by physical interaction with release-competent secretory granules.
“Biophysical measurements of exocytosis (capacitance measurements) and secretion studies on β-cell-specific knockouts of L-type Ca2+ channel subunits suggest that Cacna1c (Cav1.2) is particularly important for 1st phase insulin secretion, possibly by physical interaction with release-competent secretory granules (603) (See Section IX.D.2).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [603]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
U.K. Prospective Diabetes Study Group (1995) · Diabetes · doi:10.2337/diab.44.11.1249 · Cited by 1,923 · see citing works
Dynamics of Insulin Secretion by the Perfused Rat Pancreas
CURRY, D. L., BENNETT, L. L., & GRODSKY, G. M. (1968) · Endocrinology · doi:10.1210/endo-83-3-572 · Cited by 601 · see citing works
Fast insulin secretion reflects exocytosis of docked granules in mouse pancreatic B-cells
Olofsson, C. S., Göpel, S. O., Barg, S., Galvanovskis, J., Ma, X., Salehi, A., Rorsman, P., & Eliasson, L. (2002) · Pflügers Archiv · doi:10.1007/s00424-002-0781-5 · Cited by 290 · see citing works
Self-citationBarg, S., Eliasson, L., Renström, E., & Rorsman, P. (2002) · Diabetes · doi:10.2337/diabetes.51.2007.s74 · Cited by 227 · see citing works
Self-citationTight coupling between electrical activity and exocytosis in mouse glucagon-secreting alpha-cells.
Barg, S., Galvanovskis, J., Göpel, S. O., Rorsman, P., & Eliasson, L. (2000) · Diabetes · doi:10.2337/diabetes.49.9.1500 · Cited by 209 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 3
- Wang,W., Xu,J. and Kirsch,T. (2002) Annexin-mediated Ca 2+ in¯ux regulates growth plate chondrocyte maturation and apoptosis. J. Biol. Chem., in press.
- Wiser,O., Trus,M., Hernandez,A., Renstro Èm,E., Barg,S., Rorsman,P. and Atlas,D. (1999) The voltage sensitive Lc-type Ca 2+ channel is functionally coupled to the exocytotic machinery. Proc. Natl Acad. Sci. USA., 96, 248±253.
- Yang,S.N. et al. (1999) Syntaxin 1 interacts with the L(D) subtype of voltage-gated Ca 2+ channels in pancreatic b cells. Proc. Natl Acad. Sci. USA, 96, 10164±10169.
Cited by
Sorted by citations
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
Self-citationCdk5-dependent regulation of glucose-stimulated insulin secretion
Wei, F.-Y., Nagashima, K., Ohshima, T., Saheki, Y., Lu, Y.-F., Matsushita, M., Yamada, Y., Mikoshiba, K., Seino, Y., Matsui, H., et al. (2005) · Nature Medicine · doi:10.1038/nm1299 · Cited by 199 · see citing works
Göpel, S., Zhang, Q., Eliasson, L., Ma, X., Galvanovskis, J., Kanno, T., Salehi, A., & Rorsman, P. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2003.059675 · Cited by 160 · see citing works
Self-citationLeung, Y. M., Kwan, E. P., Ng, B., Kang, Y., & Gaisano, H. Y. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0010 · Cited by 106 · see citing works
Insulin secretion from beta cells in intact mouse islets is targeted towards the vasculature
Low, J. T., Zavortink, M., Mitchell, J. M., Gan, W. J., Do, O. H., Schwiening, C. J., Gaisano, H. Y., & Thorn, P. (2014) · Diabetologia · doi:10.1007/s00125-014-3252-6 · Cited by 89 · see citing works
- Authors
- Schulla, V., Renström, E., Feil, R., Feil, S., Franklin, I., Gjinovci, A., Jing, X., Laux, D., Lundquist, I., Magnuson, M. A., Obermüller, S., Olofsson, C. S., Salehi, A., Wendt, A., Klugbauer, N., Wollheim, C. B., Rorsman, P., & Hofmann, F.
- Affiliations
- Technical University of Munich (DE)
- Lund University (SE)
- University Hospital of Geneva (CH)
- Vanderbilt University (US)
- Corresponding author
- Renström, Erik
- ORCID
- Venue
- The EMBO Journal
- Published
- 2003-08-01
- Volume
- 22
- Issue
- 15
- Pages
- 3844-3854
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC169062
- OpenAlex
- W2136358674
- Cited by
- 234
- References
- 6
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 11 · 2023: 4 · 2022: 10 · 2021: 15 · 2020: 3 · 2019: 12 · 2018: 5 · 2017: 11 · 2016: 6 · 2015: 5 · 2014: 19 · 2013: 8 · 2012: 8
- FWCI
- 16.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- European Commission
- Deutsche Forschungsgemeinschaft
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (66907)
- Vetenskapsrådet
- 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
- Cav1.2, L-type calcium channels, insulin secretion, glucose tolerance, first-phase insulin secretion, exocytosis, calcium influx, pancreatic beta cells, intracellular calcium homeostasis
- MeSH terms
- Insulin Secretion, Animals, Base Sequence, Exocytosis, Insulin, Insulin Resistance, Islets of Langerhans, DNA Primers, Calcium Channels, L-Type, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
