The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Loss of Connexin36 Channels Alters β-Cell Coupling, Islet Synchronization of Glucose-Induced Ca2+ and Insulin Oscillations, and Basal Insulin Release
Abstract
Normal insulin secretion requires the coordinated functioning of β-cells within pancreatic islets. This coordination depends on a communications network that involves the interaction of β-cells with extracellular signals and neighboring cells. In particular, adjacent β-cells are coupled via channels made of connexin36 (Cx36). To assess the function of this protein, we investigated islets of transgenic mice in which the Cx36 gene was disrupted by homologous recombination. We observed that compared with wild-type and heterozygous littermates that expressed Cx36 and behaved as nontransgenic controls, mice homozygous for the Cx36 deletion (Cx36−/−) featured β-cells devoid of gap junctions and failing to exchange microinjected Lucifer yellow. During glucose stimulation, islets of Cx36−/− mice did not display the regular oscillations of intracellular calcium concentrations ([Ca2+]i) seen in controls due to the loss of cell-to-cell synchronization of [Ca2+]i changes. The same islets did not release insulin in a pulsatile fashion, even though the overall output of the hormone in response to glucose stimulation was normal. However, under nonstimulatory conditions, islets lacking Cx36 showed increased basal release of insulin. These data show that Cx36-dependent signaling is essential for the proper functioning of β-cells, particularly for the pulsatility of [Ca2+]i and insulin secretion during glucose stimulation.
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In the citing paper
“and in connexin-36 KO mice, synchronized [Ca2+]i oscillations are no longer observed at the whole-islet level (537).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [537]
In the citing paper
“Connexin-36 (Gjd2/GJD2) is the only connexin expressed at significant levels in either mouse or human islets (Appendix Figure 10), and in connexin-36 KO mice, synchronized [Ca2+]i oscillations are no longer observed at the whole-islet level (537).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [537]
Citations
Cites
Autonomic regulation of islet hormone secretion - Implications for health and disease
Åhrén, B. (2000) · Diabetologia · doi:10.1007/s001250051322 · Cited by 929
Deans, M. R., Gibson, J. R., Sellitto, C., Connors, B. W., & Paul, D. L. (2001) · Neuron · doi:10.1016/s0896-6273(01)00373-7 · Cited by 579
Impaired Pulsatile Secretion of Insulin in Relatives of Patients with Non-Insulin-Dependent Diabetes
O'Rahilly, S., Turner, R. C., & Matthews, D. R. (1988) · New England Journal of Medicine · doi:10.1056/nejm198805123181902 · Cited by 540
Glucose Sensing in Pancreatic β-Cells
Schuit, F. C., Huypens, P., Heimberg, H., & PIPELEERS, D. G. (2001) · Diabetes · doi:10.2337/diabetes.50.1.1 · Cited by 415
The preparation of, and studies on, free cell suspensions from mouse pancreatic islets
Lernmark, Å. (1974) · Diabetologia · doi:10.1007/bf01221634 · Cited by 357
Santos, R. M., Rosario, L. M., Nadal, A., Garcia-Sancho, J., Soria, B., & Valdeolmillos, M. (1991) · Pfl�gers Archiv European Journal of Physiology · doi:10.1007/bf00550880 · Cited by 350 · cited 1×
“These oscillations are caused by a depolarizationmediated, periodic influx of Ca(2) into -cells (22,23), as shown by their temporal relation with membrane potential changes (17,21) and their abolition by the omission of extracellular Ca(2) , blockers of L-type Ca(2) channels, or membrane repolarization (17,22).”
BackgroundGilon, P., Shepherd, R. M., & Henquin, J. C. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41522-0 · Cited by 329
Self-citationExpression of Connexin36 in the adult and developing rat brain
Belluardo, N., Mudò, G., Salinaro, A. T., Gurun, S. L., Charollais, A., Serre‐Beinier, V., Amato, G., Haefliger, J., Meda, P., & Condorelli, D. F. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02300-3 · Cited by 281
Self-citationBrief, Irregular Oscillations of Basal Plasma Insulin and Glucose Concentrations in Diabetic Man
Lang, D. A., Matthews, D. R., Burnett, M., & Turner, R. C. (1981) · Diabetes · doi:10.2337/diab.30.5.435 · Cited by 279
Selective Impairment of Hippocampal Gamma Oscillations in Connexin-36 Knock-Out MouseIn Vivo
Buhl, D. L., Harris, K. D., Hormuzdi, S. G., Monyer, H., & Buzsáki, G. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-03-01013.2003 · Cited by 269
Cited by
Sorted by citations
The unique cytoarchitecture of human pancreatic islets has implications for islet cell function
Cabrera, O., Berman, D. M., Kenyon, N. S., Ricordi, C., Berggren, P.-O., & Caicedo, A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510790103 · Cited by 1,312
Islet Amyloid Polypeptide, Islet Amyloid, and Diabetes Mellitus
Westermark, P., Andersson, A., & Westermark, G. T. (2011) · Physiological Reviews · doi:10.1152/physrev.00042.2009 · Cited by 1,044
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
Regulation of insulin secretion: a matter of phase control and amplitude modulation
Henquin, J. C. (2009) · Diabetologia · doi:10.1007/s00125-009-1314-y · Cited by 513
Self-citationThe cell biology of systemic insulin function
Tokarz, V. L., MacDonald, P. E., & Klip, A. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201802095 · Cited by 471
“Gap junction coupling between β-cells via connexin36 plays a critical role, the loss of which results in dysregulation of insulin secretion (Ravier et al., 2005).”
Background
Metadata
- Authors
- Ravier, M. A., Güldenagel, M., Charollais, A., Gjinovci, A., Caille, D., Söhl, G., Wollheim, C. B., Willecke, K., Henquin, J.-C., & Meda, P.
- Affiliations
- UCLouvain (BE)
- Institute of Genetics, University of Bonn, Bonn, Germany
- University of Geneva (CH)
- Department of Cell Physiology and Metabolism, Geneva University Medical Center, Geneva, Switzerland
- University of Bonn (DE)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2005-06-01
- Volume
- 54
- Issue
- 6
- Pages
- 1798-1807
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2108896758
- Cited by
- 360
- References
- 52
- Citations by year
- 2026: 11 · 2025: 8 · 2024: 12 · 2023: 19 · 2022: 20 · 2021: 28 · 2020: 19 · 2019: 12 · 2018: 10 · 2017: 19 · 2016: 18 · 2015: 19 · 2014: 26 · 2013: 24 · 2012: 25
- FWCI
- 16.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK63443, R01DK063443)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- connexin 36, gap junctions, pancreatic islets, insulin secretion, calcium oscillations, insulin oscillations, glucose-stimulated insulin secretion
- MeSH terms
- Gap Junction delta-2 Protein, Animals, Calcium, Female, Glucose, Heterozygote, Homozygote, Insulin, Islets of Langerhans, Male, Connexins, Mice, Knockout, Mice
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