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Pro-Survival Role of Gelsolin in Mouse ß-Cells

From the Department of Genetic Medicine and Development, University Medical Center, Geneva, Switzerland

Address correspondence and reprint requests to Barbara Yermen, Department of Genetic Medicine and Development, University Medical Center, 1 rue Michel-Servet, 1211 Geneva-4, Switzerland. E-mail: Barbara.Yermen{at}medecine.unige.ch

Abbreviations: Control-RNAi, pSUPER-Control RNA interface; GFP, green fluorescent protein; Gsn-RNAi, pSUPER–gelsolin RNAi; HA, hemagglutinin; HA-Gsn, pcDNA3.1-HA-gelsolin; HRP, horseradish peroxidase; IL-1ß, interleukin-1ß; shRNA, small hairpin RNA; siRNA, small interfering RNA; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; VDAC, voltage-dependent anion channel

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 ß-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 (B1>>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 ß-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 ß-cells.

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