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© 2014 The Authors. 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.

Original publication

DOI

10.1016/j.celrep.2014.11.010

Type

Journal article

Journal

Cell Reports

Publication Date

01/01/2014

Volume

9

Pages

2206 - 2218