ArticleCell metabolism2009
Suppression of sulfonylurea- and glucose-induced insulin secretion in vitro and in vivo in mice lacking the chloride transport protein ClC-3.
Article in Cell metabolism, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 52 citations in OpenAlex.
- Molecular requirements of chromogranin B for the long-sought anion shunter of regulated secretion.International journal of biological macromolecules · 2025Article
- Structural basis of adenine nucleotides regulation and neurodegenerative pathology in ClC-3 exchanger.Nature communications · 2024Article
- Article
- Vesicular CLC chloride/proton exchangers in health and diseases.Frontiers in pharmacology · 2023Review
- Epigenetic and transcriptomic alterations in the ClC-3-deficient mice consuming a normal diet.Frontiers in cell and developmental biology · 2023Article
- Inside the Insulin Secretory Granule.Metabolites · 2021Review
- Islet Function in the Pathogenesis of Cystic Fibrosis-Related Diabetes Mellitus.Clinical medicine insights. Endocrinology and diabetes · 2021Review
- Chloride transporters and channels in β-cell physiology: revisiting a 40-year-old model.Biochemical Society transactions · 2019Review
- Clcn3 deficiency ameliorates high-fat diet-induced obesity and adipose tissue macrophage inflammation in mice.Acta pharmacologica Sinica · 2019Article
- Glutamate as intracellular and extracellular signals in pancreatic islet functions.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2019Review
- Glibenclamide-Induced Autophagy Inhibits Its Insulin Secretion-Improving Function inInternational journal of endocrinology · 2019Article
- Activation of GLP-1 receptor signalling alleviates cellular stresses and improves beta cell function in a mouse model of Wolfram syndrome.Diabetologia · 2018Article
- Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men.Physiological reviews · 2018Review
- Review
- Ionic mechanisms in pancreatic β cell signaling.Cellular and molecular life sciences : CMLS · 2014Review
- Glutamate acts as a key signal linking glucose metabolism to incretin/cAMP action to amplify insulin secretion.Cell reports · 2014Article
- Glucose-induced electrical activities and insulin secretion in pancreatic islet β-cells are modulated by CFTR.Nature communications · 2014Article
- CFTR and Anoctamin 1 (ANO1) contribute to cAMP amplified exocytosis and insulin secretion in human and murine pancreatic beta-cells.BMC medicine · 2014Article
- GLP-1 receptor activated insulin secretion from pancreatic β-cells: mechanism and glucose dependence.Diabetes, obesity & metabolism · 2013Review
- Dynamics of insulin secretion and the clinical implications for obesity and diabetes.The Journal of clinical investigation · 2011Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Priming of insulin secretory granules for release requires intragranular acidification and depends on vesicular Cl(-)-fluxes, but the identity of the chloride transporter/ion channel involved is unknown. We tested the hypothesis that the chloride transport protein ClC-3 fulfills these actions in pancreatic beta cells. In ClC-3(-/-) mice, insulin secretion evoked by membrane depolarization (high extracellular K(+), sulfonylureas), or glucose was >60% reduced compared to WT animals. This effect was mirrored by a approximately 80% reduction in depolarization-evoked beta cell exocytosis (monitored as increases in cell capacitance) in single ClC-3(-/-) beta cells, as well as a 44% reduction in proton transport across the granule membrane. ClC-3 expression in the insulin granule was demonstrated by immunoblotting, immunostaining, and negative immuno-EM in a high-purification fraction of large dense-core vesicles (LDCVs) obtained by phogrin-EGFP labeling. The data establish the importance of granular Cl(-) fluxes in granule priming and provide direct evidence for the involvement of ClC-3 in the process.
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