Pancreatic islets from dexamethasone-treated rats show alterations in global gene expression and mitochondrial pathways

Autor(es)

Roma, Leticia P. ^{[1, 2]} ; Souza, Kleber L. A. ^[2] ; Carneiro, Everardo M. ^[2] ; Boschero, Antonio C. ^[2] ; Bosqueiro, Jose R. ^[3]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, BR-05880900 Sao Paulo - Brazil

^[2] State Univ Campinas UNICAMP, Inst Biol, Dept Physiol & Biophys, Lab Endocrine Pancreas & Metab, Campinas, SP - Brazil

^[3] Sao Paulo State Univ UNESP, Fac Sci, Dept Phys Educ, Lab Endocrine Pancreas Physiol, Bauru, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: GENERAL PHYSIOLOGY AND BIOPHYSICS; v. 31, n. 1, p. 65-76, MAR 2012.
• Citações Web of Science: 10

Resumo

Chronic administration of glucocorticoids (GC) leads to characteristic features of type 2 diabetes in mammals. The main action of dexamethasone in target cells occurs through modulation of gene expression, although the exact mechanisms are still unknown. We therefore investigated the gene expression profile of pancreatic islets from rats treated with dexamethasone using a cDNA array screening analysis. The expression of selected genes and proteins involved in mitochondria] apoptosis was further analyzed by PCR and immunoblotting. Insulin, triglyceride and free fatty acid plasma levels, as well as glucose-induced insulin secretion, were significantly higher in dexamethasone-treated rats compared with controls. Out of 1176 genes, 60 were up-regulated and 28 were down-regulated by dexamethasone treatment. Some of the modulated genes are involved in apoptosis, stress response, and proliferation pathways. RT-PCR confirmed the cDNA array results for 6 selected genes. Bax alpha protein expression was increased, while Bcl-2 was decreased. In vivo dexamethasone treatment decreased the mitochondrial production of NAD(P)H, and increased ROS production. Concluding, our data indicate that dexamethasone modulates the expression of genes and proteins involved in several pathways of pancreatic-islet cells, and mitochondria dysfunction might be involved in the deleterious effects after long-term GC treatment. (AU)

• Processo FAPESP: 04/14494-6 - Protecao das celulas produtoras de insulina por enzimas varredoras de radicais livres: participacao do sistema de peroxirredoxinas e possivel sinergismo com a prolactina.
• Beneficiário: Kleber Luiz de Araujo e Souza
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado