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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2007.tde-05112007-163505
Document
Author
Full name
Rosana Cristina Tieko Mori
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2007
Supervisor
Committee
Machado, Ubiratan Fabres (President)
Fortes, Zuleica Bruno
Giannella, Maria Lucia Cardillo Correa
Moises, Regina Celia Mello Santiago
Nascimento, Claudia Maria da Penha Oller do
Title in Portuguese
Glimepirida melhora a sensibilidade à insulina em ratos obesos (MSG), sem exacerbar a obesidade. Mecanismos moleculares envolvidos nos tecidos muscular, adiposo e hepático.
Keywords in Portuguese
Glimepirida Obesidade
GLUT4
GSK-3
Resistência à insulina
Abstract in Portuguese
O estudo investigou a ação sensibilizadora à insulina da glimepirida (Gp), em ratos MSG, resistentes à insulina. Animais controle (C) e MSG, e tratados (CG e MSG/G) ou não com Gp, foram submetidos a ITT; análise do GLUT4 no tecido adiposo (TAB), EDL, sóleo e coração; ensaios de translocação e captação de glicose/incorporação ao glicogênio no sóleo; dosagem do glicogênio e p-GSK3 no fígado. No TAB, mRNA e proteína GLUT4 se elevaram nos MSG, o que foi revertido pela Gp, efeito importante para não agravar a obesidade. No sóleo, o mRNA aumentou nos MSG, mas a proteína GLUT4 foi igual a C, e se elevou com a Gp. Sob estímulo insulínico, GLUT4 em membranas plasmáticas aumentou em ratos C e MSG/G. Captação de glicose e incorporação ao glicogênio muscular no sóleo, conteúdo de glicogênio e de p-GSK3 no fígado foram menores nos MSG. A Gp aumentou a expressão/translocação de GLUT4 em músculo de ratos MSG, melhorando a captação de glicose e glicogeniogênese neste tecido. Estes efeitos, mais o aumento da glicogeniogênese hepática, conferem à Gp ação sensibilizadora à insulina.
Title in English
Glimeiride improves insulin sensitivity in MSG obese rats, without aggravating the obesity. Molecular mechanisms involved in muscular, adipose and hepatic tissues.
Keywords in English
Glimepiride
GLUT4
GSK-3
Insulin resistance
Obesity
Abstract in English
The study investigated the insulin sensitizer action of the glimepiride (Gp) in insulin- resistant MSG rats. Control (C) and MSG animals, non-treated or treated with Gp (CG and MSG/G) were submitted to ITT; GLUT4 analysis in adipose tissue (WAT), EDL, soleus and heart; GLUT4 translocation assays and glucose uptake/glycogen incorporation in soleus; glycogen and p-GSK3 analysis in the liver. In WAT, GLUT4 mRNA and protein increase in MSG rats was abolished by Gp, an effect important to avoid the aggravation of the obesity. In MSG soleus, GLUT4 mRNA increased but protein was similar to C, elevating after Gp. Under insulin stimulation, GLUT4 in plasma membrane increased in C and MSG/G only. Glucose uptake and incorporation to muscular glycogen in soleus, and glycogen/p-GSK-3 content in the liver were all lower in MSG rats. Gp increased GLUT4 expression/translocation in MSG muscle, improving glucose uptake and glycogenesis in this tissue. These effects, added to the higher hepatic glycogenesis confer the Gp its insulin sensitizer action.
 
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Publishing Date
2007-11-06
 
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