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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“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
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Levitt, C. H., Isaacs, D. P., Hansen, M. S., Kravets, V. V., Briggs, J. K., & Benninger, R. K. P. (2026) · The Journal of General Physiology · doi:10.1085/jgp.202513867 · Cited by 2
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Martinez, C., Maschio, D. A., de Fontes, C. C., Vanzela, E. C., Benfato, I. D., Gazarini, M. L., Carneiro, E. M., de Oliveira, C. A. M., Collares‐Buzato, C. B., & Carvalho, C. P. D. F. (2022) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/j.aanat.2022.151891 · Cited by 3
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Волкова, Н. И., Davidenko, I. Y., Николаевич, Г. С., Shebeko, S. K., & Kirichenko, E. Y. (2025) · Ural Medical Journal · doi:10.52420/umj.24.4.7 · Cited by 1
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Juszczak, G. R., & Swiergiel, A. H. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-415901-3.00016-5 · Cited by 1
Klee, P., & Meda, P. (2012) · médecine/sciences · doi:10.1051/medsci/2012281015 · Cited by 1
Self-citationChen, P., Wu, C., Lu, D.-H., Sumi, S., Lin, F., & Yang, K. (2012) · Process Biochemistry · doi:10.1016/j.procbio.2012.11.016 · Cited by 1
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Sato, H., & Uzu, M. (2015) · Folia Pharmacologica Japonica · doi:10.1254/fpj.145.74 · Cited by 1
Calcium Signaling in the Islets
Islam, M. S. (2014) · Springer eBooks · doi:10.1007/978-94-007-6686-0_9 · Cited by 1
Impact of diabetes on cellular connections: Pathological insights and emerging therapeutic targets
Kanwal, A., Kanwar, N., Shetty, M. P., Rana, K., Alisi, A., Bhatia, A., & Bharati, S. (2025) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2025.103300 · Cited by 1
Tamarit‐Rodriguez, J. (2025) · Cells · doi:10.3390/cells14211644 · Cited by 1
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Patwardhan, J., & Peercy, B. E. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11469-2 · Cited by 1
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Nyqvist, D. (2007) · Figshare · Cited by 1
Current trends in type 1 diabetes mellitus--stem cells and beyond.
Hingorjo, M. R., Syed, S., Qureshi, M. A., & Kumar, A. (2007) · PubMed · Cited by 1
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Ren, H., Li, Y., Han, C., Yu, Y., Shi, B., Peng, X., Wu, S., Yang, X., Sneppen, K., Chen, L., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.16.252304 · Cited by 1
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Anderson, R. L. (2011) · Nottingham ePrints (University of Nottingham)
Accounting for Near-Normal Glucose Sensitivity in Kir6.2[AAA] Transgenic Mice
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Christian, D. A. (2014) · Research Commons (University of Waikato)
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Xi, Y., & Haj, F. G. (2013) · Springer eBooks · doi:10.1007/978-1-4614-7855-3_3
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Veenstra, R. D. (2015) · Springer series in biophysics · doi:10.1007/978-3-319-20149-8_13
Live Imaging of Neural Cell Functions
Bavamian, S., Scemes, E., & Meda, P. (2009) · Springer protocols handbooks/Springer protocols · doi:10.1007/978-1-60761-292-6_22
Self-citationParacrine regulation of glucagon secretion from pancreatic islets
Elliott, A. D. (2014)
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Islam, M. S. (2014) · Springer eBooks · doi:10.1007/978-94-007-6884-0_9-2
Current literature in diabetes
(2006) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.640
Berney, T., Andrès, A., Wassmer, C., & Berishvili, E. (2023) · Springer eBooks · doi:10.1007/978-3-031-20999-4_84
Hauke, S., Keutler, K., Laguerre, A., Carbo, M. A., Rada, J., Grandy, D. K., Yushchenko, D. A., & Schultz, C. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.21.585773
Leonhardt, L., Folias, A. E., & Hebrok, M. (2026) · Springer eBooks · doi:10.1007/978-3-031-96019-2_21
Goswami, I., Koepke, J. P., Baghelani, M., MacDonald, P. E., Kravets, V. V., Light, P. E., & Edwards, A. G. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.27.708039
Etude génétique du contrôle glycémique
Bonnefond, A. (2010) · theses.fr (ABES) · doi:10.70675/4e9cd6bdza386z40e4z92faz9ac2313560c5
Zhuang, S.-Y., Lu-jin, X., Yang, H.-X., Yang, Q.-W., Chen, G., Xu, B., Yu, Z., Liu, Y., & Xu, T.-C. (2026) · World Journal of Methodology · doi:10.5662/wjm.118207
Pfabe, J. U., Cambraia, A., Dadi, P. K., Cutler, M., dos Santos, C., Acree, C., Habashy, A., Perkins, G. A., Ellisman, M. H., Jacobson, D. A., et al. (2026) · Cell Calcium · doi:10.1016/j.ceca.2026.103161 · Cited by 1
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Grubelnik, V., & Marhl, M. (2026) · Metabolites · doi:10.3390/metabo16070462
Xie, Y., Postić, S., Pereyra, D., Ferrara, R., Mullins, A., Pfabe, J. U., Dalman, M., Hallin, K., Ingvast, S., Smith, N., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.30.735261
Pérez-Armendáriz, E. M., Zacarías-Lara, O., Revilla, M., Page-Pérez, E. R., Hernández‐Téllez, B., Zarain‐Herzberg, Á., Flores‐García, C. A., Arreola-Rosales, R. L., & Gudiño‐Zayas, M. (2026) · Bioscience Reports · doi:10.1042/bsr20250223
Camara, L. R. P., & Vilas‐Boas, E. A. (2026) · Frontiers in Network Physiology · doi:10.3389/fnetp.2026.1864821
Traveling chimeras and collective coordination in β -cell networks
Anonymous, Meli, V. N., Louodop, P., Tsakou, S. B., & Njougouo, T. (2026) · Physical review. E · doi:10.1103/3v5l-pgzz · Cited by 1
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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