%0 Journal Article 
%A Baena Nieto, Gloria
%A Lomas Romero, Isabel M.
%A Mateos Bernal, Rosa María
%A Leal Cosme, Noelia
%A Pérez Arana, Gonzalo Martín
%A Aguilar Diosdado, Manuel
%A Segundo Iglesias, María del Carmen
%A Lechuga Sancho, Alfonso María
%T Ghrelin mitigates β-cell mass loss during insulitis in an animal model of autoimmune diabetes mellitus, the BioBreeding/Worcester rat
%D 2017
%@ 1520-7560

%U http://hdl.handle.net/10498/36629
%X 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 β-cell. Given the immunomodulating effects of ghrelin and its trophic effects on β-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. β-cell mass, islet area, islet number, β-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 < 0.0001). It decreased islet infiltration and partially prevented β-cell mass loss, enabling the maintenance of β-cell neogenesis and proliferation rates. Furthermore, ghrelin treatment did not induce any metabolic perturbations. Conclusions: These findings support the hypothesis that ghrelin delays the development of autoimmune diabetes by attenuating insulitis and supporting β-cell mass. General Significance: Ghrelin promotes β-cell viability and function through diverse mechanisms that may have significant implications for diabetes prevention, therapy and also transplant success of both islets and complete pancreas.
%K ghrelin
%K autoimmne
%K prevention
%K β-cell viability
%K cytokines
%K type 1 diabetes
%~ Universidad de Cádiz