@article{Piccand:2014:10.1016/j.celrep.2014.11.033,
author = {Piccand, J and Strasser, P and Hodson, DJ and Meunier, A and Ye, T and Keime, CL and Birling, MC and Rutter, GA and Gradwohl, GJ},
doi = {10.1016/j.celrep.2014.11.033},
journal = {Cell Reports},
pages = {2219--2232},
title = {Rfx6 Maintains the Functional Identity of Adult Pancreatic β Cells},
url = {http://dx.doi.org/10.1016/j.celrep.2014.11.033},
volume = {9},
year = {2014}
}

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TY  - JOUR
AB  - Increasing evidence suggests that loss of β cell characteristics may cause insulin secretory deficiency indiabetes, but the underlying mechanisms remain unclear. Here, we show that Rfx6, whose mutation leads to neonatal diabetes in humans, is essential to maintain key features of functionally mature β cells in mice. Rfx6 loss in adult β cells leads to glucose intolerance, impaired β cell glucose sensing, and defective insulin secretion. This is associated with reduced expression of core components of the insulin secretion pathway, including glucokinase, the Abcc8/SUR1 subunit of KATP channels and voltage-gated Ca2+ channels, which are direct targets of Rfx6. Moreover, Rfx6 contributes to the silencing of the vast majority of "disallowed" genes, a group usually specifically repressed in adult β cells, and thus to the maintenance of β cell maturity. These findings raise the possibility that changes in Rfx6 expression or activity may contribute to β cell failure in humans.
AU  - Piccand,J
AU  - Strasser,P
AU  - Hodson,DJ
AU  - Meunier,A
AU  - Ye,T
AU  - Keime,CL
AU  - Birling,MC
AU  - Rutter,GA
AU  - Gradwohl,GJ
DO  - 10.1016/j.celrep.2014.11.033
EP  - 2232
PY  - 2014///
SN  - 2211-1247
SP  - 2219
TI  - Rfx6 Maintains the Functional Identity of Adult Pancreatic β Cells
T2  - Cell Reports
UR  - http://dx.doi.org/10.1016/j.celrep.2014.11.033
UR  - http://hdl.handle.net/10044/1/19807
VL  - 9
ER  - 

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