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Doctoral Thesis
DOI
10.11606/T.42.2009.tde-09022010-102039
Document
Author
Full name
Ricardo Zanuto Pereira
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Carvalho, Carla Roberta de Oliveira (President)
Caperuto, Luciana Chagas
Cipolla Neto, Jose
Hirata, Aparecida Emiko
Silva, Silvana Auxiliadora Bordin da
Title in Portuguese
A suplementação com melatonina promove melhora nas etapas iniciais da sinalização insulínica no hipotálamo, fígado, músculo esquelético e tecido adiposo em ratos velhos e obesos, precedendo a perda de peso
Keywords in Portuguese
Envelhecimento
Insulina
Intracelular
Melatonina
Obesidade.
Abstract in Portuguese
No presente estudo, analisamos a regulação das etapas iniciais da ação insulínica através de imunoprecipitação e imunobloting do tecido hipotalâmico, hepático, adiposo e músculo esquelético de ratos idosos tratados cronicamente com melatonina. O tratamento crônico com melatonina induziu aumento da sensibilidade à insulina acompanhada de regulação positiva das etapas iniciais da ação do hormônio em hipotálamo, fígado, músculo esquelético e tecido adiposo de ratos com 13 meses de idade. Os efeitos da ação da melatonina sobre a sinalização insulínica também ocorreu de forma tecido-específica, de maneira semelhante aos efeitos pleiotrópicos da insulina. Nosso estudo reafirma o papel da melatonina como um fator regulador da ação insulínica e permitem a conclusão de que a reposição desse hormônio pode contribuir com a reversão da resistência à insulina e redução do peso corporal que acompanha o processo normal de envelhecimento.
Title in English
Melatonin supplementation to obese and aged rats induces up-regulation of the insulin intracellular signaling pathway in the hypothalamus, liver, skeletal muscle and adipose tissue preceding weight loss
Keywords in English
Aging
Insulin
Intracellular
Melatonin
Obesity.
Abstract in English
Melatonin can negate several morphological and metabolic aged-induced changes. Although, this has been known for some time, the mechanism underlying melatonins actions are unclear. As suggested by some studies, a putative interaction between insulin and melatonin could be involved. In the present study, we have examined the regulation of the insulin signaling pathways by using immunoprecipitation and immunoblotting in hypothalamus, liver, adipose tissue and skeletal muscle of aged rats chronically treated with melatonin. Melatonin treatment promoted increase in insulin sensitivity and a reduction of visceral fat. These modifications were accompanied by the increased phosphorylation of insulin signaling downstream compounds associated with food ingestion in hypothalamus, glucose homeostasis in liver and adipose tissue (e.g. IRS-1) and mitogenic action on insulin in skeletal muscle (e.g. ERK-1/2). These results indicate that, in aged rats, melatonin regulates insulin signaling downstream components in a tissue-specific manner.
 
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Publishing Date
2010-03-15
 
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