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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2018.tde-21022018-172243
Document
Author
Full name
Caio Yogi Yonamine
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Machado, Ubiratan Fabres (President)
Festuccia, William Tadeu Lara
Giannella, Maria Lucia Cardillo Correa
Ortis, Fernanda
Silva, Maria Elizabeth Rossi da
Title in Portuguese
O Diabetes Mellitus induz alterações epigenéticas no gene Slc2a4 em músculo esquelético que se relacionam com a repressão do gene, e que podem ser revertidas pela insulinoterapia ou pelo resveratrol.
Keywords in Portuguese
Acetilação de histona H3
Diabetes mellitus
Epigenética
Resveratrol
SIRT1
Trimetilação de histona H3
Abstract in Portuguese
A principal característica do diabetes mellitus (DM) é a perda da homeostasia glicêmica. O músculo esquelético desempenha papel chave e a adequada expressão do transportador de glicose GLUT4 (gene Slc2a4) é fundamental. Regulações epigenéticas do Slc2a4, como acetilação/trimetilação de histona H3, nunca foram investigadas no DM; e o resveratrol, sugerido como sensibilizador da insulina, poderia modular essas regulações, pois ativa a desacetilase sirtuína 1 (SIRT1). O objetivo foi avaliar em modelos de DM o efeito do tratamento com resveratrol sobre a homeostasia glicêmica, a expressão de Slc2a4/GLUT4 em músculo esquelético, a regulação epigenética do Slc2a4, e a possível participação da SIRT1. Os dados revelam a ocorrência de regulações epigenéticas no gene Slc2a4 em músculo de animais diabéticos e mostra que o tratamento com insulina ou resveratrol modula algumas dessas alterações, melhorando o controle glicêmico. Esses resultados apoiam o resveratrol como um sensibilizador da insulina, e constroem bases para o desenvolvimento de terapias epigenéticas para o DM.
Title in English
Diabetes Mellitus induces epigenetic alterations in the slc2a4 gene in skeletal muscle that relate to gene repression and can be reversed by insulinotherapy or resveratrol.
Keywords in English
Slc2a4
Diabetes mellitus
Epigenetic
GLUT4
Histone H3 acetylation
Histone H3 methylation
Resveratrol
SIRT1
Abstract in English
The main characteristic of diabetes mellitus (DM) is the loss of glycemic homeostasis. The skeletal muscle plays a key role and the maintenance expression of the GLUT4 glucose transporter (encoded by the Slc2a4 gene) is fundamental. Epigenetic regulations of Slc2a4, such as histone H3 acetylation/trimethylation, have never been investigated in DM; and resveratrol, suggested as an insulin sensitizer, could modulate these regulations, as it is an activator of the deacetylase sirtuin 1 (SIRT1). The aim was to evaluate in skeletal muscle of diabetic animals the effect of resveratrol treatment on glycemic homeostasis, Slc2a4/GLUT4 expression in skeletal muscle, the epigenetic regulation of Slc2a4, and the possible participation of SIRT1. The data reveals the occurrence of epigenetic regulation in the Slc2a4 gene in muscle of diabetic animals and the insulin or resveratrol treatment modulates some of these changes, improving glycemic control. These results support resveratrol as an insulin sensitizer, and build bases for the development of epigenetic therapies for DM.
 
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Release Date
2020-02-22
Publishing Date
2018-02-22
 
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