Abstract 240: Effect of Co-Administration of Simvastatin and Pioglitazone on Lipid Profile and Insulin Resistance in Insulin-Resistant Rats

Abstract

Objective: Insulin resistance is characterized by hyperglycemia, dyslipidemia, hyperinsulinemia and hypertension. Also, in obesity, decreased plasma adiponectin and increased free fatty acids, are the main factors that correlate with insulin resistance. Thiazolidinediones, like pioglitazone are used to improve insulin sensitivity and ATPIII guidelines suggest statin therapy for correction of dyslipidemia in metabolic syndrome. In this study we evaluated co-administration of simvastatin and pioglitazone on insulin resistance in rats. Materials and Methods: Rats were randomly divided into five groups. After 6 weeks on a high-fructose diet, one group received simvastatin, one group received pioglitazone, and one received pioglitazone and simvastatin. After 2 weeks of treatment, animals were anesthetized with ether. Blood was collected from their heart. Liver, visceral adipose, and muscle tissues were collected and were immediately frozen. Serum glucose, TGs, cholesterol, insulin, adiponectin, and free fatty acids were measured. Expression of PPAR.γ and GLUT4 genes was checked by real-time PCR and Western blotting. Results: Only the results that showed a significant difference are shown. Blood glucose: pioglitazone group (129.1±5.8mg/dl), simvastatin-pioglitazone treated group (137.1±9.9 mg/dl); TG: simvastatin group (123.6±16.6 mg/dl), simvastatin-pioglitazone group (101.5±7.5 mg/dl); Insulin: pioglitazone group (40.27±2.75 p mol/l), simvastatin group (70.07±10.35 pmol/l), simvastatin-pioglitazone (47.62±2.8 pmol/l); Adiponectin: pioglitazone (5.90±0.29 μg/ml), simvastatin-pioglitazone (5.89±0.41μg/ml); HOMA-IR: pioglitazone (2.11±0.13), simvastatin (4.76±0.37), simvastatin-pioglitazone (2.70±0.29). In pioglitazone group, PPAR.γ expression at both mRNA and protein levels was significantly different from insulin resistant group. Conclusion: As the results show, simvastatin has beneficial effects on insulin resistance in rats. Pioglitazone did not show any synergistic effect with simvastatin, however, when used in combination with simvastatin, pioglitazone shows a synergistic effects in lowering TG and HOMAIR that potentially can lower diabetes complications.