2018
DOI: 10.1038/s41467-017-02664-0
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SWELL1 is a glucose sensor regulating β-cell excitability and systemic glycaemia

Abstract: Insulin secretion is initiated by activation of voltage-gated Ca2+ channels (VGCC) to trigger Ca2+-mediated insulin vesicle fusion with the β-cell plasma membrane. The firing of VGCC requires β-cell membrane depolarization, which is regulated by a balance of depolarizing and hyperpolarizing ionic currents. Here, we show that SWELL1 mediates a swell-activated, depolarizing chloride current (ICl,SWELL) in both murine and human β-cells. Hypotonic and glucose-stimulated β-cell swelling activates SWELL1-mediated IC… Show more

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Cited by 75 publications
(122 citation statements)
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References 65 publications
(114 reference statements)
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“…Our efforts to delete CDK1 were frustrated by the embryonic lethality of mice lacking ␤-cell CDK1 (CDK1-floxed mice (36); Ins1-Cre mice (37)) and by the inefficacy of Ins1-CreER mice (Jax 026802) (37) to catalyze loxP excision. Inconsistent outcomes with Ins1-CreER mice are becoming widely known, 6 although there are published successes (38). Even so, direct complex I inhibition with rotenone mimicked the effect of CDK1 inhibition on islet respiration, NADH utilization, ATP/ADP, and calcium influx.…”
Section: Discussionmentioning
confidence: 99%
“…Our efforts to delete CDK1 were frustrated by the embryonic lethality of mice lacking ␤-cell CDK1 (CDK1-floxed mice (36); Ins1-Cre mice (37)) and by the inefficacy of Ins1-CreER mice (Jax 026802) (37) to catalyze loxP excision. Inconsistent outcomes with Ins1-CreER mice are becoming widely known, 6 although there are published successes (38). Even so, direct complex I inhibition with rotenone mimicked the effect of CDK1 inhibition on islet respiration, NADH utilization, ATP/ADP, and calcium influx.…”
Section: Discussionmentioning
confidence: 99%
“…Therefore, subsequent studies employed conditional, region-and cell type-specific Lrrc8a gene deletion. This approach revealed tissue-specific contributions of VRAC to reproductive function (spermatogenesis), regulation of adipocyte size, insulin signaling, glucose homeostasis, and innate immunity (Luck et al 2018;Bao et al 2018;Zhang et al 2017;Kang et al 2018;Zhou et al 2020). Although the central nervous system (CNS) has long been considered to be the tissue with the highest sensitivity to cell volume alterations and VRAC activity (Kimelberg and Mongin 1998;Kimelberg 2005;Mongin 2007;Mongin 2016;Wilson and Mongin 2018), few studies have analyzed the functional significance of LRRC8 proteins in the brain.…”
Section: Introductionmentioning
confidence: 99%
“…Since the molecular structure of VRAC was identified, a series of antibodies against different regions of the basic subunits of the family LRRC8 have been developed and effectively used [4,5,9,14,17,18,[23][24][25][26]. Before now, VRAC subunit proteins were detected mostly by immunoblotting of the solubilized whole cells [27][28][29][30][31][32], less often of cell membranes lysates [14,33,34] or by imaging cells that have been permeabilized for staining [35,36]. Furthermore, these data were mostly obtained from cells specifically rich in VRAC such as epithelial cells, astrocytes, vascular smooth muscle cells and transfected cells.…”
Section: Discussionmentioning
confidence: 99%