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Doctoral Thesis
DOI
10.11606/T.42.2017.tde-08052017-110946
Document
Author
Full name
Danilo Antônio Corrêa Pinto Júnior
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Machado, Ubiratan Fabres (President)
Ortis, Fernanda
Passarelli, Marisa
Seelaender, Marilia Cerqueira Leite
Silveira, Leonardo dos Reis
Title in Portuguese
Efeito da albumina modificada por glicação avançada sobre a expressão do gene SLC2A4 em músculo esquelético.
Keywords in Portuguese
Slc2a4
Diabetes
GLUT4
NFKB
Produtos de glicação avançada
Abstract in Portuguese
A participação dos produtos de glicação avançada (AGEs) nas complicações crônicas relacionadas ao diabetes, têm sido muito investigadas. Entretanto, pouco se sabe sobre a participação direta dos AGEs em relação a homeostase glicêmica, na qual o transportador de glicose GLUT4 (proteína codificada pelo gene SLC2A4 ) desempenha um papel essencial. Portanto o objetivo do presente estudo é investigar o papel dos AGEs tanto in vivo quanto in vitro sobre a expressão do Slc2a4/GLUT4. Nos modelos in vivo e in vitro, os AGEs reduziram a expressão gênica/proteica do Slc2a4/GLUT4 e reduziram a sensibilidade insulínica no modelo in vivo, como também exarcebaram tanto a via inflamatória pelo NFKB quanto a via do estresse de retículo endoplasmático pelas chaperonas. Por fim, estes resultados sugerem os AGEs como um mecanismo repressor da expressão do Slc2a4/GLUT4 no músculo esquelético pelas vias de estresse de retículo e inflamatória.
Title in English
Effect of albumin modified by advanced glycation in gene expression of SLC2A4 in skeletal muscle.
Keywords in English
Slc2a4
Advanced glycation end products
Diabetes
GLUT4
NFKB
Abstract in English
The participation of advanced glycation end products (AGEs) in the diabetes-related chronic complications has been extensively investigated. However, little is known about AGEs participation in glycemic homeostasis, for which the glucose transporter GLUT4 (Slc2a4 gene) plays a key role. The aim of this study was indentify the effect of AGEs in an in vivo and in vitro models in Slc2a4/GLUT4 expression. In vivo and in vitro models showed decrease of Slc2a4/GLUT4 expression and insulin sensitivity (only on in vivo model). AGEs increase inflammatory and endoplasmic reticulum stress ways by NFKB and chaperones respectively. In sume, The results reveal that AGEs repress Slc2a4/GLUT4 expression in muscle, in a reticulum endoplasmic stress- and inflammatory-mediated way. This effect contributes to impair plasma glucose clearance, highlighting AGEs reduction/inhibition as a target to improve glycemic control in diabetes.
 
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Release Date
2019-05-08
Publishing Date
2017-05-08
 
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