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Reference: Chandra, V, Albagli-Curiel, O, Hastoy, B et al., (2014). RFX6 Regulates Insulin Secretion by Modulating Ca(2+) Homeostasis in Human β Cells. Cell reports, 9 (6), 2206-2218.Citable link to this page:

 

RFX6 Regulates Insulin Secretion by Modulating Ca(2+) Homeostasis in Human β Cells.

Abstract: Development and function of pancreatic β cells involve the regulated activity of specific transcription factors. RFX6 is a transcription factor essential for mouse β cell differentiation that is mutated in monogenic forms of neonatal diabetes. However, the expression and functional roles of RFX6 in human β cells, especially in pathophysiological conditions, are poorly explored. We demonstrate the presence of RFX6 in adult human pancreatic endocrine cells. Using the recently developed human β cell line EndoC-βH2, we show that RFX6 regulates insulin gene transcription, insulin content, and secretion. Knockdown of RFX6 causes downregulation of Ca(2+)-channel genes resulting in the reduction in L-type Ca(2+)-channel activity that leads to suppression of depolarization-evoked insulin exocytosis. We also describe a previously unreported homozygous missense RFX6 mutation (p.V506G) that is associated with neonatal diabetes, which lacks the capacity to activate the insulin promoter and to increase Ca(2+)-channel expression. Our data therefore provide insights for understanding certain forms of neonatal diabetes.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's versionNotes:Copyright © 2014 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Bibliographic Details

Publisher: Cell Press

Publisher Website: http://www.cell.com/

Journal: Cell reportssee more from them

Publication Website: http://www.cell.com/cell-reports

Issue Date: 2014-12

pages:2206-2218Identifiers

Urn: uuid:297fd546-abbc-4837-820b-8fafcb201cf5

Source identifier: 500683

Eissn: 2211-1247

Doi: https://doi.org/10.1016/j.celrep.2014.11.010 Item Description

Type: Journal article;

Language: eng

Version: Publisher's version Tiny URL: pubs:500683

Relationships





Autor: Chandra, V - - - Albagli-Curiel, O - - - Hastoy, B - - - Piccand, J - - - Randriamampita, C - - - Vaillant, E - - - Cavé, H - -

Fuente: https://ora.ox.ac.uk/objects/uuid:297fd546-abbc-4837-820b-8fafcb201cf5



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