Inhibition of apoptosis by survivin improves transplantation of pancreatic islets for treatment of diabetes in mice
Department of Cancer Biology; Department of Surgery
Animals; *Apoptosis; Cell Line; Diabetes Mellitus; Gene Expression Regulation; Humans; Islets of Langerhans; *Islets of Langerhans Transplantation; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microtubule-Associated Proteins; Neoplasm Proteins
Life Sciences | Medicine and Health Sciences
Survivin is a cancer gene implicated in inhibition of apoptosis and regulation of mitosis, but its function in normal cells has remained elusive. Here, we show that transgenic mice expressing survivin in pancreatic islet beta-cells show no changes in cell proliferation, as determined by islet size or islet number. Transplantation of survivin transgenic islets in diabetic recipient mice affords long-term engraftment and stable correction of hyperglycaemia. This involves intrinsic inhibition of beta-cell apoptosis, in vivo, and global transcriptional changes in pancreatic islets with upregulation of stress response genes, antagonists of cytokine signalling and promoters of angiogenesis. These broad cytoprotective functions of survivin in vivo might be beneficial for gene therapy of diabetes.
DOI of Published Version
EMBO Rep. 2006 Apr;7(4):438-43. Epub 2006 Feb 10. Link to article on publisher's site
Dohi, Takehiko; Salz, Whitney; Costa, Marco R.; Ariyan, Charlotte; Basadonna, Giacomo P.; and Altieri, Dario C., "Inhibition of apoptosis by survivin improves transplantation of pancreatic islets for treatment of diabetes in mice" (2006). Open Access Articles. 508.