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Doctoral Thesis
DOI
10.11606/T.42.2012.tde-17042013-095205
Document
Author
Full name
Felipe Natali Almeida
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Carvalho, Carla Roberta de Oliveira (President)
Caperuto, Luciana Chagas
Carneiro, Everardo Magalhães
Lima, Fabio Bessa
Ortis, Fernanda
Title in Portuguese
Desidroepiandrosterona  (DHEA) e envelhecimento: mecanismos celulares do efeito potencializador sobre a secreção de insulina.
Keywords in Portuguese
Envelhecimento
Glicose
Insulina
Pâncreas
Ratos
Abstract in Portuguese
Objetivamos identificar os efeitos celulares pelo qual o DHEA melhora a função das ilhotas pancreáticas. Ratos wistar com 12-14 meses de idade receberam uma única injeção subcutânea de DHEA (10mg.kg-1) ou veículo. Após uma semana, ilhotas pancreáticas foram isoladas para realização dos testes: secreção de insulina, respiração mitocondrial, oxidação de glicose, atividade da citrato sintase, fragmentação de DNA, expressão gênica e dosagem plasmáticas de hormônios esteróides sexuais. DHEA apresentou melhoria significativa na secreção de insulina. Notou-se um aumento na oxidação da glicose, respiração mitocondrial, atividade da citrato sintase, expressão do PCNA mRNA e reduzida apoptose. O uso de inibidores de receptores de andrógeno e estrógeno inibiu a secreção de insulina estimulada por glicose. Concluímos que o DHEA é capaz de melhorar a funcionalidade metabólica e reduzir o índice de apoptose da ilhota pancreática, melhorando a capacidade secretora, sendo este papel modulado, provavelmente, pela ligação do DHEA aos receptores de andrógenos e estrógenos.
Title in English
Dehydroepiandrosterone (DHEA) and aging: cellular mechanisms of the potentiating effect on insulin secretion.
Keywords in English
Aging
Glucose
Insulin
Mice
Pancreas
Abstract in English
We sought to identify the cellular effects by which DHEA improves pancreatic islets function. Male Wistar rats, 12-14 month-old, receive one subcutaneous injection of DHEA (10mg.kg-1) or vehicle. After a week, pancreatic islets from these animals were isolated and submitted to the following tests: insulin secretion, mitochondrial respiration, glucose oxidation, citrate synthase activity, DNA fragmentation, gene expression and the dosage of plasmatic steroid hormones. DHEA treatment resulted in significant improvement in insulin secretion. We observed an increase in glucose oxidation, mitochondrial respiration, citrate synthase activity, PCNA mRNA expression, and reduced apoptosis. Glucose-stimulated insulin secretion was inhibited by androgen and estrogen receptor inhibitors. We conclude that DHEA is capable of improving metabolic functionality and reduces apoptosis index in pancreatic islets, improving the secretory capacity stimulated by different secretagogues, with this being probably modulated by the binding of DHEA to androgen and estrogen receptors.
 
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Publishing Date
2013-05-21
 
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