Table of Contents Author Guidelines Submit a Manuscript
International Journal of Endocrinology
Volume 2015, Article ID 235727, 11 pages
Research Article

Ghrelin’s Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality

1Research Unit, Puerta del Mar University Hospital, 11009 Cadiz, Spain
2Department of Endocrinology and Nutrition, Jerez de la Frontera General Hospital, 11407 Jerez de la Frontera, Spain
3Andalusian Cellular Reprogramming Laboratory, 41092 Sevilla, Spain
4Genetics and Molecular Biology Research Institute, University of Valladolid-CSIC, 47003 Valladolid, Spain
5Salus Infirmorum Faculty of Nursing, Cadiz University, 11001 Cadiz, Spain
6Department of Maternal and Pediatric Medicine and Radiology, Pediatrics Unit, Puerta del Mar University Hospital, 11009 Cadiz, Spain

Received 25 March 2015; Revised 5 June 2015; Accepted 18 June 2015

Academic Editor: Sabrina Corbetta

Copyright © 2015 Antonia Diaz-Ganete et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.