详细记录  
题名:Induction of beta-Cell Replication by a Synthetic HNF4alpha Antagonist.
作者:LEE SH; PIRAN R; KEINAN E; PINKERTON A; LEVINE F;
来源:Stem Cells. 2013 Nov;31(11):2396-407. doi: 10.1002/stem.1496. [ IF= 0.00 ] ]
URL :10.1002/stem.1496
日期:20131203
摘要:Increasing the number of beta cells is critical to a definitive therapy for
diabetes. Previously, we discovered potent synthetic small molecule antagonists
of the nuclear receptor transcription factor HNF4alpha. The natural ligands of
HNF4alpha are thought to be fatty acids. Because obesity, in which there are high
circulating levels of free fatty acids, is one of the few conditions leading to
beta-cell hyperplasia, we tested the hypothesis that a potent HNF4alpha
antagonist might stimulate beta-cell replication. A bioavailable HNF4alpha
antagonist was injected into normal mice and rabbits and beta-cell ablated mice
and the effect on beta-cell replication was measured. In normal mice and rabbits,
the compound induced beta-cell replication and repressed the expression of
multiple cyclin-dependent kinase inhibitors, including p16 that plays a critical
role in suppressing beta-cell replication. Interestingly, in beta-cell ablated
mice, the compound induced alpha- and delta-cell, in addition to beta-cell
replication, and beta-cell number was substantially increased. Overall, the data
presented here are consistent with a model in which the well-known effects of
obesity and high fat diet on beta-cell replication occur by inhibition of
HNF4alpha. The availability of a potent synthetic HNF4alpha antagonist raises the
possibility that this effect might be a viable route to promote significant
increases in beta-cell replication in diseases with reduced beta-cell mass,
including type I and type II diabetes. Stem Cells 2013;31:2396-2407.

================  评  论  部  分=================

重要性:
分类:(参照 Faculty of 1000 的分类体系)


评语:

评论密码:   返回前页  [全部]