RT journal article
T1 Ghrelin mitigates β-cell mass loss during insulitis in an animal model of autoimmune diabetes mellitus, the BioBreeding/Worcester rat
A1 Baena Nieto, Gloria
A1 Lomas Romero, Isabel M.
A1 Mateos Bernal, Rosa María
A1 Leal Cosme, Noelia
A1 Pérez Arana, Gonzalo Martín
A1 Aguilar Diosdado, Manuel
A1 Segundo Iglesias, María del Carmen
A1 Lechuga Sancho, Alfonso María
A2 Anatomía PatológicaBiología Celular, Histología, Historia de la Ciencia, Medicina Legal y Forense y Toxicología
A2 Anatomía y Embriología Humana
A2 BiomedicinaBiotecnología y Salud Pública
A2 Cirugía
A2 Materno-Infantil y Radiología
A2 Medicina
K1 ghrelin
K1 autoimmne
K1 prevention
K1 β-cell viability
K1 cytokines
K1 type 1 diabetes
AB 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.
PB John Wiley and Sons Ltd
SN 1520-7560
YR 2017
FD 2017
LK http://hdl.handle.net/10498/36629
UL http://hdl.handle.net/10498/36629
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 21-sep-2026