| First Author | Jiang Y | Year | 2008 |
| Journal | Diabetes | Volume | 57 |
| Issue | 10 | Pages | 2718-27 |
| PubMed ID | 18599523 | Mgi Jnum | J:141886 |
| Mgi Id | MGI:3819992 | Doi | 10.2337/db08-0170 |
| Citation | Jiang Y, et al. (2008) Postnatal expansion of the pancreatic beta-cell mass is dependent on survivin. Diabetes 57(10):2718-27 |
| abstractText | 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. |
