Effects of Statins on Insulin-Like Growth Factor-1 Gene Expression in Fructose Induced Metabolic Syndrome in Rats

Background and Purpose: Insulin-like growth factor-1 (IGF-1) was found to have a role in both glucose homeostasis and cardiovascular disease. The present study was designed to compare the effects of fluvastatin and metformin on IGF-1 mRNA expression within the liver and on other individual components of the metabolic syndrome induced in rats by high fructose feeding. Experimental Approach: Rats fed 60% fructose in diet for 6 weeks were treated daily with fluvastatin (3.75mg/kg/day) or metformin (200mg/kg/day) during the last 2 weeks and compared with untreated fructose fed group. Fasting levels of plasma cholesterol, triglyceride, glucose, insulin, nitric oxide products, IGF-1 and IGF-1 mRNA within the liver as well as systolic blood pressure and body weight were determined. Results: Compared to control rats, the fructose fed group developed hypertension, hyperlipidemia, hyperinsulinemia, hyperglycemia and endothelial dysfunction as well as decreased levels of plasma IGF-1 and its mRNA within the liver. Fructose fed rats treated with fluvastatin or metformin for 2 weeks showed significant decrease in plasma cholesterol, triglyceride, insulin and glucose levels compared to untreated fructose fed group. Also, both drugs increased significantly plasma levels of nitric oxide products and IGF-1 together with significant increase in IGF-1 mRNA within the liver. However, only metformin treated rats showed significant decrease in systolic blood pressure compared to fructose fed group. Conclusions: This study showed that in a rat model of insulin resistance, fluvastatin improves the metabolic profile and increases plasma level of IGF-1 and its gene expression as effective as metformin.