HealthDay News — In obese canines, bilateral renal denervation (RDN) normalizes hepatic insulin sensitivity (SI) by reducing hepatic gluconeogenic genes, according to a study published recently in Diabetes.

Malini S. Iyer, PhD, from the Cedars-Sinai Diabetes and Obesity Research Institute in Los Angeles, and colleagues measured SI using euglycemic hyperinsulinemic clamp before and after six weeks of high-fat diet (HFD), and after either RDN or sham surgery. 

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The researchers found that insulin resistance was induced in the liver after HFD. This insulin resistance persisted in sham animals, while RDN completely normalized hepatic SI in fat-fed dogs; normalization was via reduction of hepatic gluconeogenic genes, including G6Pase, PEPCK, and FOXO1. Upregulation of the liver-X-receptor via the natriuretic peptide pathway was the main mechanism for down-regulation of hepatic gluconeogenesis.

“In conclusion, bilateral RDN completely normalizes hepatic SI in obese canines,” the authors write. “These preclinical data implicate a novel mechanistic role for the renal nerves in the regulation of insulin action specifically at the level of the liver and show that the renal nerves constitute a putative new therapeutic target to counteract insulin resistance.”

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