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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2015.tde-07122015-194240
Document
Author
Full name
Edson Alves de Lima Junior
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Rosa Neto, José Cesar (President)
Lira, Fábio Santos de
Ortis, Fernanda
Title in Portuguese
Doxorrubicina causa intolerância à glicose mediada pela inibição da sinalização da AMPk no músculo esquelético.
Keywords in Portuguese
AMPk
Doxorrubicina
Intolerância à glicose
Músculo esquelético
Quimioterapia
Resistência à insulina
Abstract in Portuguese
O câncer é considerado uma das principais causas de morte no mundo. Para o tratamento dessa doença, frequentemente são utilizadas estratégias farmacológicas baseadas na intervenção quimioterápica, no qual a doxorubicina (DOX) é largamente utilizada. Visto que, o músculo esquelético possui importante papel na captação de glicose, o objetivo do presente trabalho foi investigar o efeito da DOX na intolerância à glicose. Para isso foram utilizados ratos Wistar, os quais receberam uma dose única de DOX ou salina intraperitoneal (15mg/kg). Avaliamos a expressão de proteínas envolvidas na sensibilidade à insulina e captação de glicose. Os ensaios captação de glicose foram realizados em cultura de miócitos, no qual foi utilizado o agonista de AMPK. O tratamento com DOX causou resistência à insulina e hiperglicemia. No músculo EDL e em miócitos houve menor expressão de GLUT-4 e de AMPk. Em conclusão, o tratamento com DOX causou intolerância à glicose e redução da expressão de AMPk e GLUT-4. A utilização do agonista de AMPk foi capaz de recuperar à intolerância à glicose.
Title in English
Doxorubicin cause glucose intolerance mediated by inhibition of AMPK signaling in skeletal muscle.
Keywords in English
AMPK
Chemotherapy
Doxorubicin
Glucose intolerance
Insulin resistance
Skeletal muscle
Abstract in English
The cancer is considered a major cause of death worldwide. For the treatment of this disease, with frequency are used pharmacological strategies based in chemotherapeutic intervention, in which doxorubicin (DOX) is widely used. Since the skeletal muscle plays an important role in glucose uptake, the aim of this study was to investigate the effect of DOX in glucose intolerance. For this Wistar rats which received a single dose of DOX or saline intraperitoneally (15mg / kg). We evaluated the expression of proteins involved in insulin sensitivity and glucose uptake. The glucose uptake assays were performed on culture myocytes, which was used in the agonist of AMPK. The treatment with DOX caused insulin resistance and hyperglycemia. In the EDL muscle myocytes and there was less expression of GLUT4 and AMPK. In conclusion, treatment with DOX caused impaired glucose tolerance and reduction of expression of AMPK and GLUT-4. The use of AMPK agonist was able to recover glucose intolerance.
 
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Publishing Date
2015-12-07
 
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