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2. Ghrelin mitigates beta-cell mass loss during insulitis in an animal model of autoimmune diabetes mellitus, the BioBreeding/Worcester rat

Author

Baena-Nieto, Gloria, Lomas-Romero, Isabel M., Mateos, Rosa M., Leal-Cosme, Noelia, Perez-Arana, Gonzalo, Aguilar-Diosdado, Manuel, Segundo, Carmen, Lechuga-Sancho, Alfonso M., [Baena-Nieto, Gloria] Puerta Mar Univ Hosp, Dept Endocrinol & Nutr, Cadiz, Spain, [Aguilar-Diosdado, Manuel] Puerta Mar Univ Hosp, Dept Endocrinol & Nutr, Cadiz, Spain, [Baena-Nieto, Gloria] Puerta Mar Univ Hosp, Res Unit, Cadiz, Spain, [Lomas-Romero, Isabel M.] Puerta Mar Univ Hosp, Res Unit, Cadiz, Spain, [Mateos, Rosa M.] Puerta Mar Univ Hosp, Res Unit, Cadiz, Spain, [Perez-Arana, Gonzalo] Puerta Mar Univ Hosp, Res Unit, Cadiz, Spain, [Lechuga-Sancho, Alfonso M.] Puerta Mar Univ Hosp, Res Unit, Cadiz, Spain, [Lomas-Romero, Isabel M.] Andalusian Cellular Reprogramming Lab, Seville, Spain, [Mateos, Rosa M.] Cadiz Univ Med Sch, Dept Biotechnol Biomedicine & Publ Hlth, Cadiz, Spain, [Leal-Cosme, Noelia] Cadiz Univ Med Sch, Dept Child & Mother Hlth, Cadiz, Spain, [Lechuga-Sancho, Alfonso M.] Cadiz Univ Med Sch, Dept Child & Mother Hlth, Cadiz, Spain, [Leal-Cosme, Noelia] Cadiz Univ Med Sch, Dept Radiol, Cadiz, Spain, [Lechuga-Sancho, Alfonso M.] Cadiz Univ Med Sch, Dept Radiol, Cadiz, Spain, [Segundo, Carmen] Univ Cadiz, Salus Infirmorum Fac Nursing, Cadiz, Spain, Andalusian Department of Health, Foundation for Biomedical Research in Cadiz, and Spanish Ministry of Education

Subjects
Inflammation, Acute-pancreatitis, type 1 diabetes, Streptozotocin, Cytokine gene-expression, Kappa-b activation, Apoptosis, autoimmne, beta-cell viability, cytokines, prevention, ghrelin, Differentiation, Unacylated ghrelin, Islets, Endocrine
Abstract

Background Ghrelin is a peptide hormone with pleiotropic effects. It stimulates cell proliferation and inhibits apoptosis-mediated cell death. It prevents diabetes mellitus in several models of chemical, surgical and biological toxic insults to pancreas in both in vivo and in vitro models and promotes glucose-stimulated insulin secretion under cytotoxic conditions. It has not yet been tested in vivo in an autoimmune model of diabetes with a persistent insult to the beta-cell. Given the immunomodulating effects of ghrelin and its trophic effects on beta-cells, we hypothesized that ghrelin treatment during the early stages of insulitis would delay diabetes onset.Methods BioBreeding/Worcester male rats received ghrelin (10 ng/kg/day) before insulitis development. Glucose metabolism was characterized by glucose and insulin tolerance tests. beta-cell mass, islet area, islet number, beta-cell clusters, proliferation and apoptosis and degree of insulitis were analysed by histomorphometry. A Kaplan-Meier survival curve was plotted and analysed applying the log-rank (Mantel-Cox) test.Results Ghrelin treatment significantly reduced the probability of developing diabetes in our model (p

Published
2017

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