Effect of renal sympathetic denervation on hepatic glucose metabolism and blood pressure in a rat model of insulin resistance

OBJECTIVE: Hypertension and diabetes are associated with impaired glucose metabolism and insulin resistance. Chronic activation of the sympathetic nervous system may contribute to either condition. The purpose of this study was to investigate the effect of renal denervation on glucose kinetics and insulin signal pathways in high-fat diet (HFD)-fed rats. METHODS: We examined the effects of renal denervation on glucose kinetics and insulin sensitivity in HFD-fed rats with a hyperinsulinemic-euglycemic clamp technique combined with [3-H] glucose and [U-C]-lactate as a tracer. We also analyzed in vivo the flux through glucose-6-phosphatase and the relative contribution of gluconeogenesis and glycogenolysis in renal denervation rats. In addition, western blotting was used to identify the activities of insulin signaling proteins. RESULTS: Renal denervation in HFD-fed rats markedly decreased blood pressure and hepatic glucose production. Hepatic glucose production reduction in renal-denervation-treated rats includes decrease in glycogenolysis by 18.2% for left renal denervation or 31.9% for bilateral renal denervation and decrease in gluconeogenesis by 16.3% for left renal denervation or 42.8% for bilateral renal denervation. These changes were accompanied by decreased hepatic expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. Importantly, renal denervation increased phosphorylation of insulin receptors, insulin receptor substrate-1 and Akt kinase in HFD-fed rats. CONCLUSION: These data corroborate the notion that renal denervation potentiates hepatic insulin sensitivity.