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

J Hypertens

aDepartment of Endocrinology, The Second Affiliated Hospital bKey Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, 400016 Chongqing cDepartment of Endocrinology, Affiliated Hospital of Zunyi Medical College, Zunyi, China dDepartment of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi, USA eSchool of Bioscience and Bioengineering, The South China University of Technology, Guangzhou, Guangdong, China.

Published: December 2016

AI Article Synopsis

  • The study investigates the effects of renal denervation on glucose metabolism and insulin signaling in rats fed a high-fat diet, particularly looking at how it impacts hypertension and insulin resistance.
  • Findings show that renal denervation significantly lowers blood pressure and reduces hepatic glucose production by decreasing both glycogenolysis and gluconeogenesis in the treated rats.
  • Additionally, renal denervation enhances insulin signaling by increasing the phosphorylation of key insulin receptors and proteins, suggesting it improves hepatic insulin sensitivity.

Article Abstract

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.

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Source
http://dx.doi.org/10.1097/HJH.0000000000001087DOI Listing

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