Postnatal Expansion of the Pancreatic \(\beta\)-Cell Mass Is Dependent on Survivin

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Postnatal Expansion of the Pancreatic \(\beta\)-Cell Mass Is Dependent on Survivin

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Title: Postnatal Expansion of the Pancreatic \(\beta\)-Cell Mass Is Dependent on Survivin
Author: Jiang, Yuying; Nishimura, Wataru; Devor-Henneman, Deborah; Kusewitt, Donna; Wang, Haijuan; Holloway, Michael P.; Dohi, Takehiko; Sabo, Edmond; Altieri, Dario C.; Altura, Rachel A.; Robinson, Michael L.; Sharma, Arun J.

Note: Order does not necessarily reflect citation order of authors.

Citation: Jiang, 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.
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Abstract: Objective: 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.
Published Version: doi://10.2337/db08-0170
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