Modulation of Fructose-Induced Insulin Resistance Syndrome in Rats by Rosiglitazone and α-Lipoic Acid

Increased fructose intake has been linked to the epidemiology of insulin resistance (IR) syndrome, type 2 diabetes mellitus, renal damage and non-alcoholic steatohepatitis. As oxidative stress plays a pivotal role in the pathology of IR, the present study was conducted to investigate the effects of rosiglitazone alone or combined with α-lipoic acid, a potent antioxidant, on fructose-induced IR syndrome in rats. Markers chosen for assessment included effects on body weight gain, glucose and insulin levels, IR, βcell function, lipid profile, nitric oxide (NO) metabolites and antioxidant status. Moreover, liver and kidney functions were assessed both biochemically and histologically. Male rats were fed with fructose-enriched diet (FED) or standard rat chow for 16 weeks. By the end of the 10 th week, FED-fed rats were divided into three groups; one was left untreated (control group) and the other 2 groups were treated p.o. with rosiglitazone (4 mg/kg) and rosiglitazone plus α-lipoic acid (100 mg/kg), respectively. Treatments continued daily for 6 weeks, afterwards blood samples were collected, animals were sacrificed and their livers and kidneys isolated. Feeding rats with FED resulted in increased weight gain, hyperinsulinemia, hyperglycemia, IR and βcell dysfunction. These changes were coupled with disturbances in lipid homeostasis, antioxidant status and alterations in NO metabolites as well as liver and kidney dysfunctions. Concomitant administration of α-lipoic acid with rosiglitazone potentiated the effects of the latter on most of the investigated parameters. In conclusion, the combination of rosiglitazone and α-lipoic could ameliorate most of the symptoms associated with IR syndrome in rats.