Effect of hepatic denervation on the counterregulatory response to insulin-induced hypoglycemia in the dog

Our aim was to determine whether complete hepatic denervation would affect the hormonal response to insulin-induced hypoglycemia in dogs. Two weeks be fore study, dogs underwent either hepatic denervation (DN) or sham denervat ion (CONT). In addition, all dogs had hollow steel coils placed around thei r vagus nerves. The CONT dogs were used for a single study in which their c oils were perfused with 37 degreesC ethanol. The DN dogs were used for two studies in a random manner, one in which their coils were perfused with -20 degreesC ethanol (DN + COOL) and one in which they were perfused with 37 d egreesC ethanol (DN). Insulin was infused to create hypoglycemia (51 +/- 3 mg/dl). In response to hypoglycemia in CONT, glucagon, cortisol, epinephrin e, norepinephrine, pancreatic polypeptide, glycerol, and hepatic glucose pr oduction increased significantly. DN alone had no inhibitory effect on any hormonal or metabolic counterregulatory response to hypoglycemia. Likewise, DN in combination with vagal cooling also had no inhibitory effect on any counterregulatory response except to reduce the arterial plasma pancreatic polypeptide response. These data suggest that afferent signaling from the l iver is not required for the normal counterregulatory response to insulin-i nduced hypoglycemia.