Exendin-4 protects rat islets against loss of viability and function induced by brain death
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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Journal Article |
| Published: |
Elsevier Ireland Ltd
2014
|
| Online Access: | http://hdl.handle.net/20.500.11937/12083 |
| _version_ | 1848747979254530048 |
|---|---|
| author | Carlessi, Rodrigo Lemos, N. Dias, A. Oliveira, F. Brondani, L. Canani, L. Bauer, A. Leitão, C. Crispim, D. |
| author_facet | Carlessi, Rodrigo Lemos, N. Dias, A. Oliveira, F. Brondani, L. Canani, L. Bauer, A. Leitão, C. Crispim, D. |
| author_sort | Carlessi, Rodrigo |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T06:57:45Z |
| format | Journal Article |
| id | curtin-20.500.11937-12083 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:57:45Z |
| publishDate | 2014 |
| publisher | Elsevier Ireland Ltd |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-120832017-09-13T14:59:51Z Exendin-4 protects rat islets against loss of viability and function induced by brain death Carlessi, Rodrigo Lemos, N. Dias, A. Oliveira, F. Brondani, L. Canani, L. Bauer, A. Leitão, C. Crispim, D. 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. 2014 Journal Article http://hdl.handle.net/20.500.11937/12083 10.1016/j.mce.2015.05.009 Elsevier Ireland Ltd unknown |
| spellingShingle | Carlessi, Rodrigo Lemos, N. Dias, A. Oliveira, F. Brondani, L. Canani, L. Bauer, A. Leitão, C. Crispim, D. Exendin-4 protects rat islets against loss of viability and function induced by brain death |
| title | Exendin-4 protects rat islets against loss of viability and function induced by brain death |
| title_full | Exendin-4 protects rat islets against loss of viability and function induced by brain death |
| title_fullStr | Exendin-4 protects rat islets against loss of viability and function induced by brain death |
| title_full_unstemmed | Exendin-4 protects rat islets against loss of viability and function induced by brain death |
| title_short | Exendin-4 protects rat islets against loss of viability and function induced by brain death |
| title_sort | exendin-4 protects rat islets against loss of viability and function induced by brain death |
| url | http://hdl.handle.net/20.500.11937/12083 |