详细记录  
题名:Involvement of the Ca2+-responsive transactivator in high glucose-induced beta-cell apoptosis.
作者:MEN X; PENG L; WANG H; ZHANG W; XU S; FANG Q; LIU H; YANG W; LOU J;
来源:J Endocrinol. 2013 Jan 18;216(2):231-43. doi: 10.1530/JOE-12-0286. Print 2013 [ IF= 0.00 ] ]
URL :10.1530/JOE-12-0286
日期:20130131
摘要:The calcium-regulated transcription coactivator, Ca(2)(+)-responsive
transactivator (CREST) was expressed in pancreatic beta-cells. Moreover, CREST
expression became significantly increased in pancreatic islets isolated from
hyperglycemic Goto-Kakizaki rats compared with normoglycemic Wistar controls. In
addition, culture of beta-cells in the presence of high glucose concentrations
also increased CREST expression in vitro. To further investigate the role of this
transactivator in the regulation of beta-cell function, we established a stable
beta-cell line with inducible CREST expression. Hence, CREST overexpression
mimicked the glucotoxic effects on insulin secretion and cell growth in
beta-cells. Moreover, high glucose-induced apoptosis was aggravated by
upregulation of the transactivator but inhibited when CREST expression was
partially silenced by siRNA technology. Further investigation found that
upregulation of Bax and downregulation of Bcl2 was indeed induced by its
expression, especially under high glucose conditions. In addition, as two causing
factors leading to beta-cell apoptosis under diabetic conditions, endoplasmic
reticulum stress and high free fatty acid, mimicked the high glucose effects on
CREST upregulation and generation of apoptosis in beta-cells, and these effects
were specifically offset by the siRNA knockdown of CREST. These results indicated
that CREST is implicated in beta-cell apoptosis induced by culture in high
glucose and hence that CREST may become a potential pharmacological target for
the prevention and treatment of type 2 diabetes mellitus.

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