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Extracellular acidification stimulates GPR68 mediated IL-8 production in human pancreatic β cells.

Abstract : Acute or chronic metabolic complications such as diabetic ketoacidosis are often associated with extracellular acidification and pancreatic β-cell dysfunction. However, the mechanisms by which human β-cells sense and respond to acidic pH remain elusive. In this study, using the recently developed human β-cell line EndoC-βH2, we demonstrate that β-cells respond to extracellular acidification through GPR68, which is the predominant proton sensing receptor of human β-cells. Using gain- and loss-of-function studies, we provide evidence that the β-cell enriched transcription factor RFX6 is a major regulator of GPR68. Further, we show that acidic pH stimulates the production and secretion of the chemokine IL-8 by β-cells through NF-кB activation. Blocking of GPR68 or NF-кB activity severely attenuated acidification induced IL-8 production. Thus, we provide mechanistic insights into GPR68 mediated β-cell response to acidic microenvironment, which could be a new target to protect β-cell against acidosis induced inflammation.
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Submitted on : Friday, August 19, 2016 - 4:04:11 PM
Last modification on : Wednesday, August 19, 2020 - 11:17:18 AM

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Vikash Chandra, Angeliki Karamitri, Paul Richards, Françoise Cormier, Cyrille Ramond, et al.. Extracellular acidification stimulates GPR68 mediated IL-8 production in human pancreatic β cells.. Scientific Reports, Nature Publishing Group, 2016, 6, pp.25765. ⟨10.1038/srep25765⟩. ⟨inserm-01354834⟩

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