Ghrelin’s Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality
Ghrelin is a peptidic hormone, which stimulates cell proliferation and inhibits apoptosis in several tissues, including pancreas. In preclinical stage of type 1 diabetes, proinflammatory cytokines generate a destructive environment for β-cells known as insulitis, which results in loss of β-cell mass...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2015/235727 |
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| author | Antonia Diaz-Ganete Gloria Baena-Nieto Isabel M. Lomas-Romero Jose Francisco Lopez-Acosta Irene Cozar-Castellano Francisco Medina Carmen Segundo Alfonso M. Lechuga-Sancho |
| author_facet | Antonia Diaz-Ganete Gloria Baena-Nieto Isabel M. Lomas-Romero Jose Francisco Lopez-Acosta Irene Cozar-Castellano Francisco Medina Carmen Segundo Alfonso M. Lechuga-Sancho |
| author_sort | Antonia Diaz-Ganete |
| collection | DOAJ |
| description | Ghrelin is a peptidic hormone, which stimulates cell proliferation and inhibits apoptosis in several tissues, including pancreas. In preclinical stage of type 1 diabetes, proinflammatory cytokines generate a destructive environment for β-cells known as insulitis, which results in loss of β-cell mass and impaired insulin secretion, leading to diabetes. Our aim was to demonstrate that ghrelin could preserve β-cell viability, turnover rate, and insulin secretion acting as a counter balance of cytokines. In the present work we reproduced proinflammatory milieu found in insulitis stage by treating murine cell line INS-1E and rat islets with a cytokine cocktail including IL-1β, IFNγ, and TNFα and/or ghrelin. Several proteins involved in survival pathways (ERK 1/2 and Akt/PKB) and apoptosis (caspases and Bcl-2 protein family and endoplasmic reticulum stress markers) as well as insulin secretion were analyzed. Our results show that ghrelin alone has no remarkable effects on β-cells in basal conditions, but interestingly it activates cell survival pathways, downregulates apoptotic mediators and endoplasmic reticulum stress, and restores insulin secretion in response to glucose when beta-cells are cytokine-exposed. These data suggest a potential role of ghrelin in preventing or slowing down the transition from a preclinical to clinically established diabetes by ameliorating the effects of insulitis on β-cells. |
| format | Article |
| id | doaj-art-780c03d93e1d4f6891dc1d4c843f89b8 |
| institution | OA Journals |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-780c03d93e1d4f6891dc1d4c843f89b82025-08-20T02:07:06ZengWileyInternational Journal of Endocrinology1687-83371687-83452015-01-01201510.1155/2015/235727235727Ghrelin’s Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell FunctionalityAntonia Diaz-Ganete0Gloria Baena-Nieto1Isabel M. Lomas-Romero2Jose Francisco Lopez-Acosta3Irene Cozar-Castellano4Francisco Medina5Carmen Segundo6Alfonso M. Lechuga-Sancho7Research Unit, Puerta del Mar University Hospital, 11009 Cadiz, SpainResearch Unit, Puerta del Mar University Hospital, 11009 Cadiz, SpainResearch Unit, Puerta del Mar University Hospital, 11009 Cadiz, SpainResearch Unit, Puerta del Mar University Hospital, 11009 Cadiz, SpainGenetics and Molecular Biology Research Institute, University of Valladolid-CSIC, 47003 Valladolid, SpainResearch Unit, Puerta del Mar University Hospital, 11009 Cadiz, SpainResearch Unit, Puerta del Mar University Hospital, 11009 Cadiz, SpainResearch Unit, Puerta del Mar University Hospital, 11009 Cadiz, SpainGhrelin is a peptidic hormone, which stimulates cell proliferation and inhibits apoptosis in several tissues, including pancreas. In preclinical stage of type 1 diabetes, proinflammatory cytokines generate a destructive environment for β-cells known as insulitis, which results in loss of β-cell mass and impaired insulin secretion, leading to diabetes. Our aim was to demonstrate that ghrelin could preserve β-cell viability, turnover rate, and insulin secretion acting as a counter balance of cytokines. In the present work we reproduced proinflammatory milieu found in insulitis stage by treating murine cell line INS-1E and rat islets with a cytokine cocktail including IL-1β, IFNγ, and TNFα and/or ghrelin. Several proteins involved in survival pathways (ERK 1/2 and Akt/PKB) and apoptosis (caspases and Bcl-2 protein family and endoplasmic reticulum stress markers) as well as insulin secretion were analyzed. Our results show that ghrelin alone has no remarkable effects on β-cells in basal conditions, but interestingly it activates cell survival pathways, downregulates apoptotic mediators and endoplasmic reticulum stress, and restores insulin secretion in response to glucose when beta-cells are cytokine-exposed. These data suggest a potential role of ghrelin in preventing or slowing down the transition from a preclinical to clinically established diabetes by ameliorating the effects of insulitis on β-cells.http://dx.doi.org/10.1155/2015/235727 |
| spellingShingle | Antonia Diaz-Ganete Gloria Baena-Nieto Isabel M. Lomas-Romero Jose Francisco Lopez-Acosta Irene Cozar-Castellano Francisco Medina Carmen Segundo Alfonso M. Lechuga-Sancho Ghrelin’s Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality International Journal of Endocrinology |
| title | Ghrelin’s Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality |
| title_full | Ghrelin’s Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality |
| title_fullStr | Ghrelin’s Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality |
| title_full_unstemmed | Ghrelin’s Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality |
| title_short | Ghrelin’s Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality |
| title_sort | ghrelin s effects on proinflammatory cytokine mediated apoptosis and their impact on β cell functionality |
| url | http://dx.doi.org/10.1155/2015/235727 |
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