RT journal article
T1 Decrease in Beta -Cell Proliferation Precedes Apoptosis during Diabetes Development in Bio-Breeding/ Worcester Rat: Beneficial Role of Exendin-4
A1 Pérez Arana, Gonzalo Martín
A1 Segundo Iglesias, María del Carmen
A1 Aguilar Diosdado, Manuel
A1 Blandino Rosano, Manuel
A1 Prada Oliveira, José Arturo
A2 Anatomía y Embriología Humana
K1 Pancreas
K1 Beta-cell mas
K1 Exendin-4
K1 Diabetes
AB In autoimmune type 1 diabetes mellitus, proinflammatory cytokine-mediated apoptosis of beta-cells has been considered to be the first event directly responsible for beta-cell mass reduction. In the Bio-Breeding (BB) rat, an in vivo model used in the study of autoimmune diabetes, beta-cell apoptosis is observed from 9 wk of age and takes place after an insulitis period that begins at an earlier age. Previous studies by our group have shown an antiproliferative effect of proinflammatory cytokines on cultured beta-cells in Wistar rats, an effect that was partially reversed by Exendin-4, an analogue of glucagon-like peptide-1. In the current study, the changes in beta-cell apoptosis and proliferation during insulitis stage were also determined in pancreatic tissue sections in normal and thymectomized BB rats, as well as in Wistar rats of 5, 7, 9, and 11 wk of age. Although stable beta-cell proliferation in Wistar and thymectomized BB rats was observed along the course of the study, a decrease in beta-cell proliferation and beta-cell mass from the age of 5 wk, and prior to the commencement of apoptosis, was noted in BB rats. Exendin-4, in combination with anti-interferon-gamma antibody, induced a near-total recovery of beta-cell proliferation during the initial stages of insulitis. This highlights the importance of early intervention and, as well, the possibilities of new therapeutic approaches in preventing autoimmune diabetes by acting, initially, in the insulitis stage and, subsequently, on beta-cell regeneration and on beta-cell apoptosis.
PB The Endocrine Society. USA
SN 0013-7227
YR 2010
FD 2010-06-01T00:00:00Z
LK http://hdl.handle.net/10498/17524
UL http://hdl.handle.net/10498/17524
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 22-sep-2026