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Inhibition of apoptosis by survivin improves transplantation of pancreatic islets for treatment of diabetes in mice.

Dohi T, Salz W, Costa M, Ariyan C, Basadonna GP, Altieri DC

Department of Cancer Biology, University of Massachusetts Medical School, Worcester, 01605, USA.

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.

Published 4 April 2006 in EMBO Rep, 7(4): 438-43.
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