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dc.contributor.authorCarlessi, Rodrigo
dc.contributor.authorLemos, N.
dc.contributor.authorDias, A.
dc.contributor.authorOliveira, F.
dc.contributor.authorBrondani, L.
dc.contributor.authorCanani, L.
dc.contributor.authorBauer, A.
dc.contributor.authorLeitão, C.
dc.contributor.authorCrispim, D.
dc.date.accessioned2017-01-30T11:28:39Z
dc.date.available2017-01-30T11:28:39Z
dc.date.created2016-03-03T19:30:22Z
dc.date.issued2014
dc.identifier.citationCarlessi, R. and Lemos, N. and Dias, A. and Oliveira, F. and Brondani, L. and Canani, L. and Bauer, A. et al. 2014. Exendin-4 protects rat islets against loss of viability and function induced by brain death. Molecular and Cellular Endocrinology. 142: pp. 239-250.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/12083
dc.identifier.doi10.1016/j.mce.2015.05.009
dc.description.abstract

Islet quality loss after isolation from brain-dead donors still hinders the implementation of human islet transplantation for treatment of type 1 diabetes. In this scenario, systemic inflammation elicited by donor brain death (BD) is among the main factors influencing islet viability and functional impairment. Exendin-4 is largely recognized to promote anti-inflammatory and cytoprotective effects on ß-cells. Therefore, we hypothesized that administration of exendin-4 to brain-dead donors might improve islet survival and insulin secretory capabilities. Here, using a rat model of BD, we demonstrate that exendin-4 administration to the brain-dead donors increases both islet viability and glucose-stimulated insulin secretion. In this model, exendin-4 treatment produced a significant decrease in interleukin-1ß expression in the pancreas. Furthermore, exendin-4 treatment increased the expression of superoxide dismutase-2 and prevented BD-induced elevation in uncoupling protein-2 expression. Such observations were accompanied by a reduction in gene expression of two genes often associated with endoplasmic reticulum (ER) stress response in freshly isolated islets from treated animals, C/EBP homologous protein and immunoglobulin heavy-chain binding protein. As ER stress response has been shown to be triggered by and to participate in cytokine-induced ß-cell death, we suggest that exendin-4 might exert its beneficial effects through alleviation of pancreatic inflammation and oxidative stress, which in turn could prevent islet ER stress and ß-cell death. Our findings might unveil a novel strategy to preserve islet quality from brain-dead donors. After testing in the human pancreatic islet transplantation setting, this approach might sum to the ongoing effort to achieve consistent and successful single-donor islet transplantation.

dc.publisherElsevier Ireland Ltd
dc.titleExendin-4 protects rat islets against loss of viability and function induced by brain death
dc.typeJournal Article
dcterms.source.issn0303-7207
dcterms.source.titleMolecular and Cellular Endocrinology
curtin.departmentSchool of Biomedical Sciences
curtin.accessStatusOpen access via publisher


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