The objective of this study was to assess the safety of surgical common hepatic artery
denervation (CHADN). This procedure has previously been shown to improve
glucose tolerance in dogs fed a high-fat high-
fructose (HFHF) diet. We assessed the
hypoglycemic response of dogs by infusing
insulin at a constant rate (1.5 mU/kg/min) for 3 h and monitoring
glucose and the counterregulatory
hormones (
glucagon,
catecholamine, and
cortisol). After an initial
hypoglycemic study, the dogs were randomly assigned to a
SHAM surgery (n = 4) or hepatic
sympathetic denervation (CHADN, n = 5) and three follow-up studies were performed every month up to 3 months after the surgery. The level of
norepinephrine (NE) in the liver and the pancreas was significantly reduced in the CHADN dogs, showing a decrease in sympathetic tone to the splanchnic organs. There was no evidence of any defect of the response to
hypoglycemia after the CHADN surgery. Indeed, the extent of
hypoglycemia was similar in the
SHAM and CHADN groups (~45 mg/dl) for the same amount of circulating
insulin (~50 µU/ml) regardless of time or surgery. Moreover the responses of the counterregulatory
hormones were similar in extent and pattern during the 3 h of
hypoglycemic challenge. Circulating
lactate,
glycerol,
free fatty acids, and
beta-hydroxybutyrate were also unaffected by CHADN during fasting conditions or during the
hypoglycemia. There were no other notable surgery-induced changes over time in nutrients, minerals, and
hormones clinically measured in the dogs nor in the blood pressure and heart rate of the animals. The data suggest that the ablation of the sympathetic nerve connected to the splanchnic bed is not required for a normal counterregulatory response to
insulin-induced
hypoglycemia and that CHADN could be a safe new therapeutic intervention to improve
glycemic control in individuals with
metabolic syndrome or
type 2 diabetes.