The Effect of Co-administration of Pioglitazone and Simvastatin on Insulin Resistance Parameters and PPAR.γ Expression in Insulin-resistant Rats

Backgrounds: Insulin resistance is a pathological condition associated with metabolic syndrome. In this condition, insulin action in liver, muscles, and adipocytes decreases which leads to hyperglycemia, hyperinsulinemia, and dyslipidemia. Thiazolidinediones (Pioglitazone) have been used to enhance insulin sensitivity but due to dyslipidemia associated with insulin resistance, adult treatment panel III (ATPIII) have suggested statin therapy for ameliorating dyslipidemia in metabolic syndrome. Method: In this study, 40 rats were randomly divided into 5 groups (8 rats per group). The first group was considered as the healthy control group and fed with regular chow. In other groups, insulin resistance was induced by feeding a high-fructose diet for 6 weeks. Then, the 2nd, 3rd and 4th groups respectively received Pioglitazone, Simvastatin and Simvastatin+Pioglitazone through gavage for 2 weeks and the 5th group (control group) did not receive any drug. At the end of the treatment period, serum samples were collected in fasting condition. The levels of glucose, triglycerides, insulin, and adiponectin were measured by ELISA method, and HOMA-IR was calculated. Animals were anesthetized to remove liver for measuring PPAR.γ expression. Results: Blood glucose in Pioglitazone group (129.1±5.8 mg/dl) and Simvastatin+Pioglitazone group (137.1±9.9 mg/dl), triglyceride in Simvastatin group (123.6±16.6 mg/dl) and Simvastatin+Pioglitazone group (101.5±7.5 mg/dl), insulin in Pioglitazone group (40.27±2.75 pmol/L), Simvastatin group (70.07±10.35 pmol/L), and Simvastatin+Pioglitazone group (47.62±2.80 pmol/L) and adiponectin in Pioglitazone group (5.90±0.29 μg/ml) and Simvastatin+Pioglitazone group (5.89±0.41 μg/ml) showed significant differences with the corresponding values in the control group [blood glucose (187.5±15.9 mg/dl), triglyceride (217.6±18.5 mg/dl), adiponectin (3.86±0.14 μg/ml), insulin (137.65±34.22 pmol/L) and HOMA-IR (9.7±2.13)]. Pioglitazone significantly increased PPAR.γ expression, but Simvastatin suppressed the effect of Pioglitazone on PPAR.γ expression. Conclusion: The results show that Simvastatin has beneficial effects on insulin resistance in rats fed with high-fructose diet, but it has no synergistic or antagonistic effect with Pioglitazone.