Jiang, YuyingNishimura, WataruDevor-Henneman, DeborahKusewitt, DonnaWang, HaijuanHolloway, Michael P.Dohi, TakehikoSabo, EdmondAltieri, Dario C.Altura, Rachel A.Robinson, Michael L.Sharma, Arun J.2013-01-242008Jiang, Yuying, Wataru Nishimura, Deborah Devor-Henneman, Donna Kusewitt, Haijuan Wang, Michael P. Holloway, Takehiko Dohi, et al. 2008. Postnatal expansion of the pancreatic \(\beta\)-cell mass is dependent on survivin. Diabetes 57(10): 2718-2727.0012-1797http://nrs.harvard.edu/urn-3:HUL.InstRepos:10212564Objective: Diabetes results from a deficiency of functional \(\beta\)-cells due to both an increase in \(\beta\)-cell death and an inhibition of \(\beta\)-cell replication. The molecular mechanisms responsible for these effects in susceptible individuals are mostly unknown. The objective of this study was to determine whether a gene critical for cell division and cell survival in cancer cells, survivin, might also be important for \(\beta\)-cells. Research Design and Methods: We generated mice harboring a conditional deletion of survivin in pancreatic endocrine cells using mice with a Pax-6-Cre transgene promoter construct driving tissue-specific expression of Cre-recombinase in these cells. We performed metabolic studies and immunohistochemical analyses to determine the effects of a mono- and biallelic deletion of survivin. Results: Selective deletion of survivin in pancreatic endocrine cells in the mouse had no discernible effects during embryogenesis but was associated with striking decreases in \(\beta\)-cell number after birth, leading to hyperglycemia and early-onset diabetes by 4 weeks of age. Serum insulin levels were significantly decreased in animals lacking endocrine cell survivin, with relative stability of other hormones. Exogenous expression of survivin in mature \(\beta\)-cells lacking endogenous survivin completely rescued the hyperglycemic phenotype and the decrease in \(\beta\)-cell mass, confirming the specificity of the survivin effect in these cells. Conclusions: Our findings implicate survivin in the maintenance of \(\beta\)-cell mass through both replication and antiapoptotic mechanisms. Given the widespread involvement of survivin in cancer, a novel role for survivin may well be exploited in \(\beta\)-cell regulation in diseased states, such as diabetes.en-USJournal Article2013-01-2410.2337/db08-0170