Pro-survival role of gelsolin in mouse β-cells

被引:25
作者
Yermen, Barbara [1 ]
Tomas, Alejandra [1 ]
Halban, Philippe A. [1 ]
机构
[1] Univ Geneva, Med Ctr, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland
关键词
D O I
10.2337/db06-0769
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We have previously shown that the Ca2+-dependent actin-severing protein gelsolin plays an important role in regulated insulin secretion. The aim of this study was to determine the role of gelsolin in beta-cell survival as it has been shown to play a dual role in apoptosis in other cell types. MIN6 subclones B1 and C3, shown previously to express gelsolin at different levels (Bl >> C3 cells), were used for this purpose. We demonstrate that B1 cells have lower levels of apoptosis and active caspase-3 when compared with C3 cells, in both standard (25 mmol/l glucose and 15% FCS) and deprived (5 mmol/l glucose and 1% FCS) conditions. Overexpression of gelsolin resulted in a decrease in the percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)(+) and active caspase-3(+) cells. Conversely, knockdown of gelsolin by RNA interference in B1 cells caused an increase in the number of TUNEL+ and active caspase-3(+) cells. Finally, the anti-apoptotic role of gelsolin was confirmed in purified primary mouse beta-cells where overexpression of gelsolin resulted in a decrease in the percentage of TUNEL+ cells. In summary, our results show for the first time that gelsolin plays a pro-survival role in pancreatic beta-cells.
引用
收藏
页码:80 / 87
页数:8
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