Effects of L-Carnitine on inducible nitric oxide synthase, insulin like growth factor-1 gene expression and insulin receptor substrate-1 in kidney tissues of insulin resistant rats induced by high fructose feeding

Abstract

Metabolism of high dietary fructose induces insulin resistance and metabolic adaptation including changes in gene expression. The present study was designed to elucidate the effects of L-Carnitine (CA) on the renal alterations as well as gene expression such as inducible Nitric Oxide Synthase (iNOS). Insulin-like Growth Factor-1(IGF-1), insulin receptor substrate-1 (IRS-1) in kidney tissues of rats fed on high fructose diet. 24 male Wister rats of body weight 120-160 g were divided into 3 groups of 8 rats each . Group 1 received control diet, while group 2 and 3, rats received high fructose diet (60 g/100 g diet). Group 3, after 2 weeks of fructose feeding animals were treated with CAR (300 mg/kg body weight/day i.p). At the end of the experimental period (30 days), serum levels of glucose, insulin, Triacylglycerol (TG) and cholesterol were determined. Renal contents of cholesterol, triacylglycerol, Malondialdehyde (MDA) and nitric oxide products were determined . Gene expressions of iNOS, IGF-1 as well as IRS-1 were also assayed in kidney tissues of the experimental rats feed on high fructose diet. Rats fed on high fructose diet showed disturbance in insulin action and formed an animal model of insulin resistance. Fructose fed rats showed increase in renal gene expression of iNOS and decrease in both IGF-1 mRNA and IRS-1 receptor compared to control rats. The administration of CA to rat model of insulin resistance, mitigated the adverse effects of fructose load. Thus the observed abnormalities in gene expression associated with fructose feeding were brought to near-normal levels as compared with untreated rats. Conclusion: L-carnitine normalized the serum and renal lipid alterations as well as gene expression (iNOS, IGF-1) and IRS-1 in this nutritional experimental model.

Key words : Insulin resistance, L-carnitine, inducible nitric oxide synthase (iNOS), growth factor-1 gene expression, insulin receptor substrate-1 (IRS-1)