Effects Of Rosiglitazone On GLUT4 Protein In Insulin Resistance Rat Skeletal Muscle

Objective: To investigate expression of glucose transporter 4 (GLUT4) in the cell membrane of skeletal muscle of high-fat-fed rats and effects of rosiglitazone on GLUT4 translocation to the plasma membrane in skeletal muscle of high-fat-fed rats .Methods: 41 male Sprague Dawley rats were randomized to receive high-fat (31) or standard chow diet (10) for 8 weeks, and feeding high-fat diet induced insulin resistance in skeletal muscle of rats. Consequently 30 high-fat-fed rats were randomized for treatment with rosiglitazone (1mg/kg), standard chow diet, or placebo (high-fat diet) in a 4 weeks trial. Overnight-fasted rats were injected with insulin (10units/kg) for 15 min. Isolated rats skeletal muscle was used for studying GLUT4 by Western blotting analysis. At the same time, plasma concentration of glucose, insulin, weight and viscero-fat were measured.Results: Feeding rats a high-fat diet for 8 weeks resulted in hyperinsulineemia, hyperglycemia, and loss of insulin sensitivity. It had significant difference (P<0.001) compared with chow-fed rats. But there had on change in weight of two groups (P>0.05). After intervention study for 4weeks, plasma concentration of insulin and weight of viscero-fat in rosiglitazone and standard chow diet groups were significantly lower than that of high-fat-fed rats, and insulin sensitive index was much higher (P<0.001). Insulin-stimulated translocation of GLUT4 to the plasma membrane in muscles of high fat-fed rats was significantly lower than that of standard chow-fed rats (52.72% P<0.001). But the defects were fully prevented by dietary rosiglitazone or standard chow diet (respectively 49.53%, 50.34%, P<0.001).Conclusion: High-fat diet-mediated insulin resistance is linked to defective insulin-stimulated translocation of GLUT4 glucose transporters to cell membrane of skeletal muscle. Rosiglitazone is an insulin-sensitizing agent that appears to prevent insulin resistance in skeletal muscle of high-fat-fed rats by selectively improving GLUT4 translocation to the plasma membrane, and the effect is equivalent to intervention of standard chow diet.