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Gap Junctions and Insulin Secretion

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Pancreatic Beta Cell in Health and Disease

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Abstract

About 30 years ago, pancreatic beta cells were shown to be connected by gap junctions and to exhibit glucose-induced oscillatory electrical activity, two features that were hypothetically linked to insulin secretion. Since then, gap junctions have been shown to be an obligatory feature of beta cells in all species and all physiological conditions studied. They are composed of connexin proteins and allow for beta-cell to beta-cell exchanges of current-carrying ions and other small cytosolic metabolites which synchronize the electrical and metabolic activity of beta cells, and recruit these cells for insulin biosynthesis and release. Together, these effects account for the significant contribution of gap junction-dependent signaling to the control of insulin secretion. More recent data suggest that gap junctions, either via the expression of connexin proteins and/or of the intercellular communications that these proteins permit, also significantly influence beta-cell growth, apoptosis, and the resistance of islets to immune attack. The mechanism(s) whereby gap junction signaling exerts these multiple effects is still obscure. Understanding this mechanism is relevant both to our understanding of the physiology of pancreatic islets and to the pathophysiology of beta-cell dysfunction in both type 1 and type 2 diabetes. Furthermore, appropriate expression of gap junctions may be a prerequisite for the engineering of surrogate insulin-producing cells and their proper three-dimensional packaging, which may be important for using these cells as a cell-based therapy for the treatment of diabetic patients. Here, we review the current status of our knowledge in this field and its exciting perspectives.

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  1. Department of Cell Physiology and Metabolism, University of Geneva, Medical School, 1 rue Michel Servet, 1211, Genève 4, Switzerland

    Philippe Klee, Sabine Bavamian, Anne Charollais, Dorothée Caille, José Cancela, Manon Peyrou & Paolo Meda

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  1. Philippe Klee
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  1. Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Susumu Seino M.D., D.M. Sci. (Professor) (Professor)

  2. Medicine and Human Genetics, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL, 60637, USA

    Graeme I. Bell Ph.D. (Louis Block Distinguished Service Professor) (Louis Block Distinguished Service Professor)

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Klee, P. et al. (2008). Gap Junctions and Insulin Secretion. In: Seino, S., Bell, G.I. (eds) Pancreatic Beta Cell in Health and Disease. Springer, Tokyo. https://doi.org/10.1007/978-4-431-75452-7_7

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