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Doctoral Thesis
DOI
10.11606/T.42.2009.tde-02022010-102636
Document
Author
Full name
Fernanda Gaspar do Amaral
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Cipolla Neto, Jose (President)
Carvalho, Carla Roberta de Oliveira
Castrucci, Ana Maria de Lauro
Giannella Neto, Daniel
Silva, Silvana Auxiliadora Bordin da
Title in Portuguese
Perfil diário e os mecanismos de produção de melatonina pela glândula pineal de ratos diabéticos por estreptozotocina.
Keywords in Portuguese
AANAT
Diabetes Mellitus
Estreptozotocina
Glândula Pineal
Mecanismos de controle celular
Melatonina (Produção)
Microdiálise
Ratos
Abstract in Portuguese
A pineal participa da sincronização do organismo pela síntese de melatonina. Diabetes é um distúrbio metabólico caracterizado por hiperglicemia. Diante da controvérsia sobre a síntese de melatonina em animais diabéticos, esse trabalho objetivou avaliar as alterações da glândula pineal mediante o diabetes induzido por STZ (60mg/kg, i.p.). Ratos wistar (250-280g, 12h/12h claro/escuro) foram utilizados em todos os procedimentos que envolveram técnicas de FACS, microdiálise, HPLC, radiometria da atividade enzimática e qPCR. Os resultados mostraram que o diabetes causa diminuição (50%) e perda do perfil mono/bifásico da síntese pineal de melatonina, que não é causada por necrose ou apoptose dos pinealócitos e reflete um desarranjo no metabolismo pineal, evidenciado pela diminuição na atividade da AANAT (55%). Observou-se também um desbalanço rítmico de fatores determinantes como a expressão do receptor ß1 e a atividade e expressão das enzimas TPH1 e HIOMT. A menor concentração de melatonina circulante pode ser um fator contribuinte para o desenvolvimento da doença.
Title in English
Pineal melatonin production in Streptozotocin-diabetic rats: mechanisms and microdialysis daily profile.
Keywords in English
AANAT
Cellular control mechanisms
Diabetes Mellitus
Melatonin (Production)
Microdialysis
Pineal
Rats
Streptozotocin
Abstract in English
The gland is involved in the organism synchronization via its hormone melatonin. Diabetes involves hyperglicemia and insulin synthesis/signaling impairment. The aim of this work was to evaluate the pineal melatonin synthesis in STZ-diabetic rats (60mg/kg, i.p.). Male wistar rats (250-280g, 12h/12h light/dark) were used as the animal model and FACS, microdialysis, HPLC, enzyme activity assay and qPCR were the techniques used to evaluate the pineal phisiology. The results show a decrease in pineal melatonin (50%) and a circadian profile impairment that were not due to necrosis or apoptosis. This finding reflects an important impairment in the pineal metabolism that was related to a decrease in AANAT activity (55%). An alteration in the rhthmicity of important factors, such as the ß1-adrenergic receptor expression and the TPH1 and HIOMT activity and expression, was also observed. This decrease in circulating melatonin may be of fundamental importance to the establishment and maintenance of diabetes.
 
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Publishing Date
2010-03-02
 
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