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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2010.tde-11012011-085253
Document
Author
Full name
Thais de Castro Barbosa
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Nunes, Maria Tereza (President)
Caperuto, Luciana Chagas
Carneiro, Everardo Magalhães
Lima, Fabio Bessa
Machado, Ubiratan Fabres
Title in Portuguese
Bases moleculares dos efeitos da suplementação crônica com arginina sobre a sensibilidade à insulina: repercussões sobre os tecidos muscular esquelético, adiposo, hepático e sobre a secreção de insulina.
Keywords in Portuguese
Arginina
Hormônio do crescimento
Metabolismo de glicose e lipídeos
Óxido nítrico
Resistência à insulina
Secreção de insulina
Abstract in Portuguese
A Arginina (Arg) regula a secreção de GH e insulina, e é o único precursor biológico do NO. Previamente demonstramos que animais tratados cronicamente com Arg (35mg/dia) desenvolvem resistência à insulina (RI), e o presente estudo investigou as suas bases moleculares. A RI baseou-se na redução da atividade e/ou expressão do IRS 1/2 e Akt, e do conteúdo de GLUT4; sendo o GH crucial na gênese desses efeitos. Doses mais elevadas de Arg (70mg/dia/30 dias), a maior geração de NO e a melhora do fluxo sangüíneo reverteram este quadro. Experimentos com células musculares demonstraram que a Arg estimula o metabolismo de glicose e lipídios, via NO/c-GMP. Esses achados indicam que a Arg pode ser benéfica para o tratamento de distúrbios metabólicos, como obesidade e DM2; e que ao estimular a secreção de GH, em doses adequadas, seria eficaz na terapia de distúrbios da secreção deste hormônio. Todavia, estudos adicionais são necessários para investigar a melhor dose e os efeitos crônicos in vivo da Arg, uma vez que o GH em excesso apresenta um efeito diabetogênico importante.
Title in English
Molecular basis of the chronic effect of arginine supplementation on insulin sensitivity: repercussion in skeletal muscles, adipose tissue, liver and on insulin secretion.
Keywords in English
Arginine
Glucose and lipid metabolism
Growth hormone
Insulin resistance
Insulin secretion
Nitric oxide
Abstract in English
Arginine (Arg) regulates the secretion of GH and insulin, and it is the main biological precursor of NO. We have previously shown that animals chronically-treated with Arg (35 mg/day) developed insulin resistance (IR), and this study investigated its molecular basis. The RI relies on the reduction of the activity and/or expression of IRS 1/2 and Akt, and of the GLUT4 content; and GH has a crucial role in the genesis of these effects. Higher doses of Arg (70 mg/dia/30 days), the increased NO generation and the improvement of the blood flow reversed the RI. Experiments with muscle cells showed that Arg stimulates glucose and lipids metabolism, via NO/c-GMP activation. These findings indicate that Arg may be beneficial for the treatment of metabolic disorders, such as obesity and T2DM, and by stimulating GH secretion, Arg can, in appropriate doses, be effective for the therapy of GH secretion disorders. However, further studies are needed to investigate the best dose and the chronic effects of Arg in vivo, since that GH in excess is potentially diabetogenic.
 
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Publishing Date
2011-05-05
 
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