Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension

Background: Feeding a high-fructose diet induces hypertension and insulin-resistance in Sprague-Dawley rats. Methods: To investigate whether insulin receptors contribute to abnormal glucose metabolism and whether their regulation is differentially regulated in different tissues, we evaluated the glycemic and insulinemic response to an oral glucose load, insulin receptor binding, and insulin receptor messengerRNA (mRNA) levels in tissues of rats that were fed either standard rat chow or a diet containing 66% fructose for 2 weeks. Results: Blood pressure and plasma triglycerides increased significantly in the fructose-fed rats, whereas body weight, fasting plasma glucose, and plasma insulin did not differ significantly from controls. Plasma glucose and insulin responses to oral glucose were significantly greater in fructose-fed than in control rats. Insulin receptor-binding characteristics were determined by an in situ autoradiographic technique associated with computerized microdensitometry. The insulin receptor number was significantly lower in both skeletal muscle and liver of fructose- fed rats as compared to controls, whereas no difference was observed in the kidney. No significant differences were found in binding affinity. Insulin receptor mRNA levels were determined by slot-blot hybridization with a cRNA probe encoding the 5 end of the rat insulin receptor cDNA. Consistent with binding data, mRNA levels were significantly lower in skeletal muscle and liver of fructose-fed rats as compared to controls, but not in the kidney. Conclusions: Decreased number of insulin receptors occurring at the level of gene expression is present in skeletal muscle and liver of fructose-fed rats and might contribute to insulin resistance in this model.