Survivin Regulation of Beta-Cell Mass Expansion Figure 3. Survivin deletion in beta cells leads to decreased beta-cell mass. (a) Male and female mutant mice exhibit decreased beta-cell mass at 2-month of age as compared to controls (n = 5 per genotype). (b) IPGTTs show that the male mutant mice (g) display higher glucose excursions compared with male controls (m) whereas the female mutant mice (%) show similar responses as female controls (&) (n = 8 per genotype). (c) Declined beta-cell number is detected in the male and female mutant mice (n = 5 per genotype). (d) Total islet number is decreased in the mutant mice compared with that in controls in both sexes, mainly due to the decreased definitive islets, with small islets remained similar (n = 5 per genotype). (e) Increased beta-cell size is observed in the mutant mice in both sexes (n = 5 per genotype). (f) Mutant mice exhibit increased beta-cell nucleus size in both sexes (n = 5 per genotype). WT, wildtype (black bars); KO, knockout (white bars). The data represent as means 6 SE. *, p,0.05;**, p,0.01vs control. doi:10.1371/journal.pone.0041976.g003 increase in beta cell number was observed following the surgery (P,0.01, Fig. 5b-d). Both the small islet and larger islet number was markedly increased within the ligated pancreas tail (P,0.05, Fig. 5e). Small islets likely represented newly formed beta cells from neogenesis whereas increment in larger islets was likely from the replication of preexisting beta cells. So both beta cell neogenesis and self-duplication of existing beta cells might contribute to the expansion of beta-cell mass after PDL. However, beta-cell mass expansion in the RIPCre+Survivinfl/ flmice at day 7 post PDL was significantly impaired compared with PLoS ONE | www.plosone.org 5 August 2012 | Volume 7 | Issue 8 | e41976