Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/18599523http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18599523http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/18599523http://purl.org/dc/terms/identifier"doi:10.2337/db08-0170"xsd:string
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/author"Jiang Y."xsd:string
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/author"Sharma A."xsd:string
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/author"Wang H."xsd:string
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/author"Kusewitt D."xsd:string
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/author"Altieri D.C."xsd:string
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/author"Altura R.A."xsd:string
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/author"Holloway M.P."xsd:string
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/author"Nishimura W."xsd:string
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/author"Robinson M.L."xsd:string
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/author"Dohi T."xsd:string
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/author"Sabo E."xsd:string
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/author"Devor-Henneman D."xsd:string
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/name"Diabetes"xsd:string
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/pages"2718-2727"xsd:string
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/title"Postnatal expansion of the pancreatic beta-cell mass is dependent on survivin."xsd:string
http://purl.uniprot.org/citations/18599523http://purl.uniprot.org/core/volume"57"xsd:string
http://purl.uniprot.org/citations/18599523http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18599523
http://purl.uniprot.org/citations/18599523http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/18599523
http://purl.uniprot.org/uniprot/#_D3Z7S6-mappedCitation-18599523http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18599523
http://purl.uniprot.org/uniprot/#_D3YWU5-mappedCitation-18599523http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18599523
http://purl.uniprot.org/uniprot/#_D3Z595-mappedCitation-18599523http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18599523
▶