caspase-9 (Cell Signaling Technology, Danvers, MA, USA). Monoclonal antibodies against a-tubulin (Sigma-Aldrich, St-Louis, MO, USA) were used to normalize the signals. siRNA design and cell transfection Specific siRNAs against rat Cdk5r2 were selected using the siRNA Target Finder (Ambion, Austin, TX, USA). The silencing efficiency of each construct was checked at the transcript level using target genes fused to a luciferase reporter gene, as previously described [13]. Two efficient siRNAs, siCdk5r2#1 (59-GCCAGC- GUCCACCGGUCCCUU-39) and siCdk5r2#2 (59-GCCACC- GUCGCUAUUACCGUU-39), and the negative siRNA(59AG- GUAGUGUAAUCGCCUUGUU-39) were synthesized from Microsynth (Balgach, Switzerland). INS-1E cells were seeded in 12-well plates and incubated overnight in antibiotic-free medium. 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