Postnatal expansion of the pancreatic β-Cell mass is dependent on survivin

Yuying Jiang, Wataru Nishimura, Deborah Devor-Henneman, Donna Kusewitt, Haijuan Wang, Michael P. Holloway, Takehiko Dohi, Edmond Sabo, Michael L. Robinson, Dario C. Altieri, Arun Sharma, Rachel A. Altura

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31 Scopus citations

Abstract

OBJECTIVE-Diabetes results from a deficiency of functional β-cells due to both an increase in β-cell death and an inhibition of β-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 β-cells. RESEARCH DESIGN AND METHODS-We generated mice harboring a conditional deletion of survivin in pancreatic endocrine cells using mice with a Pαx-6-Cre transgene promoter construct driving tissue-specific expression of Cre-recombinase in these cells. We performed metabolic studies and immuno-histochemical 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 β-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 β-cells lacking endogenous survivin completely rescued the hyperglycemic phenotype and the decrease in β-cell mass, confirming the specificity of the survivin effect in these cells. CONCLUSIONS-Our findings implicate survivin in the maintenance of β-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 β-cell regulation in diseased states, such as diabetes.

Original languageEnglish (US)
Pages (from-to)2718-2727
Number of pages10
JournalDiabetes
Volume57
Issue number10
DOIs
Publication statusPublished - Oct 1 2008

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All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Jiang, Y., Nishimura, W., Devor-Henneman, D., Kusewitt, D., Wang, H., Holloway, M. P., ... Altura, R. A. (2008). Postnatal expansion of the pancreatic β-Cell mass is dependent on survivin. Diabetes, 57(10), 2718-2727. https://doi.org/10.2337/db08-0170