Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/106708
Type: Artigo de periódico
Title: Increased Pancreatic Islet Mass Is Accompanied By Activation Of The Insulin Receptor Substrate-2/serine-threonine Kinase Pathway And Augmented Cyclin D2 Protein Levels In Insulin-resistant Rats
Author: Rafacho A.
Ribeiro D.L.
Boschero A.C.
Taboga S.R.
Bosqueiro J.R.
Abstract: It is well known that glucocorticoids induce peripheral insulin resistance in rodents and humans. Here, we investigated the structural and ultrastructural modifications, as well as the proteins involved in beta-cell function and proliferation, in islets from insulin-resistant rats. Adult male Wistar rats were made insulin resistant by daily administration of dexamethasone (DEX; 1mg/kg, i.p.) for five consecutive days, whilst control (CTL) rats received saline alone. Structure analyses showed a marked hypertrophy of DEX islets with an increase of 1.7-fold in islet mass and of 1.6-fold in islet density compared with CTL islets (P < 0.05). Ultrastructural evaluation of islets revealed an increased amount of secreting organelles, such as endoplasmic reticulum and Golgi apparatus in DEX islets. Mitotic figures were observed in DEX islets at structural and ultrastructural levels. Beta-cell proliferation, evaluated at the immunohistochemical level using anti-PCNA (proliferating cell nuclear antigen), showed an increase in pancreatic beta-cell proliferation of 6.4-fold in DEX islets compared with CTL islets (P < 0.0001). Increases in insulin receptor substrate-2 (IRS-2), phosphorylated-serine-threonine kinase AKT (p-AKT), cyclin D2 and a decrease in retinoblastoma protein (pRb) levels were observed in DEX islets compared with CTL islets (P < 0.05). Therefore, during the development of insulin resistance, the endocrine pancreas adapts itself increasing beta-cell mass and proliferation, resulting in an amelioration of the functions. The potential mechanisms that underlie these events involve the activation of the IRS-2/AKT pathway and activation of the cell cycle, mediated by cyclin D2. These adaptations permit the maintenance of glycaemia at near-physiological ranges. © 2008 The Authors.
Editor: 
Rights: fechado
Identifier DOI: 10.1111/j.1365-2613.2008.00588.x
Address: http://www.scopus.com/inward/record.url?eid=2-s2.0-47649101647&partnerID=40&md5=bd62f9a5889e8c80d09a9a40ef361b2d
Date Issue: 2008
Appears in Collections:Unicamp - Artigos e Outros Documentos

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