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
A1 Blandino-Rosano, Manuel
A1 Prada-Oliveira, Arturo
A1 Aguilar-Diosdado, Manuel
A1 Segundo, Carmen
K1 Agentes hipoglucémicos
K1 Péptidos
K1 Veneno
K1 Exenatida
K1 Interferon-gamma
K1 Diabetes Mellitus
K1 Anticuerpos
K1 Animales
K1 Ratas Wistar
K1 Distribución aleatoria
K1 Células secretoras de insulina
K1 Inmunohistoquímica
K1 Test de tolerancia a la glucosa
K1 Péptido glucagonoide 1
K1 Proliferación celular
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 Endocrine Society
SN 0013-7227
YR 2010
FD 2010-06-01
LK http://hdl.handle.net/10668/727
UL http://hdl.handle.net/10668/727
LA en
NO Pérez-Arana G, Blandino-Rosano M, Prada-Oliveira A, Aguilar-Diosdado M, Segundo C. Decrease in {beta}-cell proliferation precedes apoptosis during diabetes development in bio-breeding/worcester rat: beneficial role of Exendin-4. Endocrinology. 2010 Jun; 151(6):2538-46
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 15, 2025