Inhibition of apoptosis by survivin improves transplantation of pancreatic islets for treatment of diabetes in mice
Open accessAbstract
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.
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Birc5 is a crucial and universal component that ensures successful expansion of β-cell mass in various conditions.
“These studies implicate Birc5 as a crucial and universal component that ensures successful expansion of β-cell mass in various conditions [60] (Figure 4).”
From Expansion of β-cell mass in response to pregnancy (2010) · cites this paper as [60]
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Expansion of β-cell mass in response to pregnancy
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- Authors
- Dohi, T., Salz, W., Costa, M., Ariyan, C., Basadonna, G. P., & Altieri, D. C.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Yale University (US)
- Corresponding author
- Altieri, Dario C
- Venue
- The EMBO Reports
- Published
- 2006-02-10
- Volume
- 7
- Issue
- 4
- Pages
- 438-443
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC1456913
- OpenAlex
- W2151825778
- Cited by
- 32
- References
- 17
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 4 · 2013: 2
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- EMBO Reports (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- National Institutes of Health (HL54131)
- National Heart, Lung, and Blood Institute (R01HL054131, R37HL054131, HL 54131)
- National Cancer Institute (R01CA078810, CA-78810, R01CA090917, CA-90917)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Keywords
- survivin, apoptosis inhibition, islet transplantation, beta-cell apoptosis, diabetes mellitus, islet engraftment, stress response genes, cytokine signaling, angiogenesis, gene therapy, transgenic mice
- MeSH terms
- Survivin, Animals, Cell Line, Diabetes Mellitus, Gene Expression Regulation, Humans, Islets of Langerhans, Mice, Inbred C57BL, Mice, Transgenic, Microtubule-Associated Proteins, Neoplasm Proteins, Repressor Proteins, Islets of Langerhans Transplantation, Apoptosis, Inhibitor of Apoptosis Proteins, Mice
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