The objective was to determine if the cervical vagus or hepatic branch of the vagus nerve is a suitable site to produce functional
parasympathetic denervation of the liver in the rat as assessed from the ability to produce
insulin resistance. Anterior plexus
denervation in both anesthetized rats and cats results in
insulin resistance as assessed by the rapid
insulin sensitivity test (RIST). This diagnostic test is a modified euglycemic clamp using the amount of
glucose required to be infused to maintain euglycemia following a bolus administration of
insulin (50 mU kg(-1) over 5 min, 0.1 ml min(-1) infusion) as the index of
insulin sensitivity. Blood sampling was achieved through an arteriovenous
silicone vascular shunt connecting the left carotid artery and the right jugular vein and allowed the close monitoring of blood glycemia throughout the test (every 2 min). The control RIST index (249.2 +/- 10.2 mg kg(-1)) was significantly decreased (P<0.001) following hepatic
vagotomy (134.0 +/- 13.9). The intraportal infusion of 2.5 microg kg(-1) min(-1) of
acetylcholine partially reversed (202.1 +/- 12.3) the
insulin resistance. Intravenous
atropine (1 mg kg(-1)) or hepatic anterior plexus
denervation did not produce significant further
insulin resistance. A similar degree of
insulin resistance was produced by bilateral cervical
vagotomy which was also partially reversed by
acetylcholine. Complete hepatic
parasympathetic denervation was achieved by selective hepatic vagal branch section. The data suggest that all of the parasympathetic nerves that regulate hormonal control of
insulin resistance pass through the cervical vagus and the hepatic branch, and finally, through the anterior hepatic plexus along the common hepatic artery and that
denervation at any of these sites leads to functional elimination of all hepatic parasympathetic input regulating
insulin sensitivity. This approach provides an additional research tool to study the hepatic parasympathetic reflex control of peripheral
insulin action.