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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Chandra V,Albagli-Curiel O,Hastoy B,Piccand J,Randriamampita C,Vaillant E,Cavé H,Busiah K,Froguel P,Vaxillaire M,Rorsman P,Polak M,Scharfmann Rdoi
10.1016/j.celrep.2014.11.010subject
Has Abstractpub_date
2014-12-24 00:00:00pages
2206-18issue
6issn
2211-1247pii
S2211-1247(14)00964-4journal_volume
9pub_type
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