Avaliação da função e plasticidade celuar de ilhotas pancreaticas em modelo de resistencia a insulina induzida por dexametosa em ratos / Analysis of dexamethasone treatment effcts on insulin secretion, molecular and biochemical parameters in submitted to protein restriction

AUTOR(ES)

Silvana Quallio

DATA DE PUBLICAÇÃO

2008

RESUMO

Introduction and aims: Insulin binds to plasma membrane receptors leading to a variety of cellular responses. Malfunction in any of the insulin cell signalling pathways in target tissues may lead to several conditions and diseases, like hyperglycemia, insulin resistance and type 2 diabetes mellitus (T2DM). These effects may be experimentally reproduced using high doses of glucocorticoids, providing thus a good model for the study of T2DM. The aims of this study were to evaluate the plasticity of pancreatic islets subject to variation on the need for insulin secretory induction of peripheral resistance to the hormone by treatment with dexamethasone and subsequent treatment interruption. Methods: Male wistar rats (90 days old) were treated with dexamethasone (1mg/kg, ip) for 5 consecutive days (DEX). In another group (DEX10), the animals were treated in the same way and assessed 10 days after the last day of administration. Control rats (CTL) received equivalent volume of vehicle. Protein expression was assayed trough immunoblotting. Morphometric analyses were done using a optical microscope and specific digital analysis programs. Results: DEX group showed marked peripheral insulin resistance, reverted after the recovering period in the DEX10 group. DEX islets showed functional and morphological changes, like increased insulin secretion, superficial area, population density, and a tendency for increase in the total mass content of beta cell. Cell cycle proteins CD2 and CDK4 and AKT phosphorylation were increased in the DEX group when compared to CTL group. All these effects were reverted in the group DEX10. Conclusions: These results show that the endocrine pancreas possess a plasticity regarding the capacity of pancreatic islets to adapt themselves to situations where a higher or lower demand for insulin is needed.

ASSUNTO(S)

dexamethasone langerhans islands of langerhans ilhotas de resistencia a insulina dexametasona insulin tolerance

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