1801-P: Common Hepatic Artery Denervation Does Not Alter the Counterregulatory Response to Hypoglycemia in an Insulin Resistant Canine Model

Abstract

With the recent interest in sympathetic modulation as a way to improve insulin sensitivity and insulin secretion, it is important to assess the safety of the procedure. Five dogs were fed a high fat high fructose diet for 5-week before undergoing a hyperinsulinemic hypoglycemic clamp (insulin infused IV at a rate of 1.5 mU/kg/min). Then the dogs underwent a common hepatic artery surgical denervation (CHAD n=5) and were studied 1, 2 and 3 months post-surgery with the same hypoglycemic challenge. At the end of the protocol, the norepinephrine content in the liver (7±3 ng/g) and pancreas (91±34 ng/g) were significantly lower than levels in the livers and pancreas of 4 sham denervated animals (460±100 and 590±93 ng/g respectively), indicating successful denervation. There were no significant differences in fasting insulin, glucose or glucagon concentrations over the 3 months (see Table). The insulin and glucose concentrations during the last 90 min of the hypoglycemic challenge prior to and post-CHAD were also not different. The peak in plasma glucagon and epinephrine levels occurred at 30 and 120 min respectively and were similar in magnitude pre- and post-CHAD. Four sham denervated animals had the same response to the insulin induced hypoglycemic challenge as CHAD dogs. In conclusion, the response to hypoglycemia was not affected by sympathetic denervation of the common hepatic artery. Disclosure G. Kraft: Consultant; Self; Metavention. L. Moore: None. B. Farmer: None. M.F. Scott: None. D.S. Edgerton: Speaker's Bureau; Self; Novo Nordisk A/S. P.E. Williams: None. B. Azamian: Employee; Self; Metavention. A.D. Cherrington: Board Member; Self; Biocon, Fractyl Laboratories, Inc., Metavention, Sensulin, LLC., vTv Therapeutics, Zafgen, Inc. Consultant; Self; Abvance, Boston Scientific Corporation, California Institute for Biomedical Research, Galvani Bioelectronics Limited, MedImmune, Novo Nordisk Inc., Thetis Pharmaceuticals LLC. Research Support; Self; Abvance, Diasome Pharmaceuticals, Inc., Novo Nordisk Inc. Stock/Shareholder; Self; Abvance, Biocon, Fractyl Laboratories, Inc., Metavention, Novo Nordisk Inc., Sensulin, LLC., Thetis Pharmaceuticals LLC, Zafgen, Inc. Funding Metavention, Inc.