Sympathetic Denervation of the Common Hepatic Artery Lessens Glucose Intolerance in the Fat- and Fructose-Fed Dog.

This study assessed the effectiveness of surgical sympathetic denervation of the common hepatic artery (CHADN) in improving glucose tolerance. CHADN eliminated norepinephrine content in the liver and partially decreased it in the pancreas and the upper gut. We assessed oral glucose tolerance at baseline and after 4 weeks of high-fat high-fructose (HFHF) feeding. Dogs were then randomized to sham surgery (SHAM) (n = 9) or CHADN surgery (n = 11) and retested 2.5 or 3.5 weeks later while still on the HFHF diet. CHADN improved glucose tolerance by ∼60% in part because of enhanced insulin secretion, as indicated by an increase in the insulinogenic index. In a subset of dogs (SHAM, n = 5; CHADN, n = 6), a hyperinsulinemic-hyperglycemic clamp was used to assess whether CHADN could improve hepatic glucose metabolism independent of a change in insulin release. CHADN reduced the diet-induced defect in net hepatic glucose balance by 37%. In another subset of dogs (SHAM, n = 4; CHADN, n = 5) the HFHF diet was continued for 3 months postsurgery and the improvement in glucose tolerance caused by CHADN continued. In conclusion, CHADN has the potential to enhance postprandial glucose clearance in states of diet-induced glucose intolerance.

The effect of vagal cooling on canine hepatic glucose metabolism in the presence of hyperglycemia of peripheral origin.

We examined the role of vagus nerves in the transmission of the portal glucose signal in conscious dogs. At time 0, somatostatin infusion was started along with intraportal insulin and glucagon at 4-fold basal and basal rates, respectively. Glucose was infused via a peripheral vein to create hyperglycemia ( approximately 2 fold basal). At t = 90, hollow coils around the vagus nerves were perfused with -10 degrees C or 37 degrees C solution in the vagally cooled (COOL) and sham-cooled (SHAM) groups, respectively (n = 6 per group). Effectiveness of vagal blockade was demonstrated by increase in heart rate during perfusion in the COOL vs SHAM groups (183 +/- 3 vs 102 +/- 5 beats per minute, respectively) and by prolapse of the third eyelid in the COOL group. Arterial plasma insulin (22 +/- 2 and 24 +/- 3 micro U/mL) and glucagon (37 +/- 5 and 40 +/- 4 pg/mL) concentrations did not change significantly between the first experimental period and the coil perfusion period in either the SHAM or COOL group, respectively. The hepatic glucose load throughout the entire experiment was 46 +/- 1 and 50 +/- 2 mg . kg(-1) . min(-1) in the SHAM and COOL groups, respectively. Net hepatic glucose uptake (NHGU) did not differ in the SHAM and COOL groups before (2.2 +/- 0.5 and 2.9 +/- 0.8 mg . kg(-1) . min(-1), respectively) or during the cooling period (3.0 +/- 0.5 and 3.4 +/- 0.6 mg . kg(-1) . min(-1), respectively). Likewise, net hepatic glucose fractional extraction and nonhepatic glucose uptake and clearance were not different between groups during coil perfusion. Interruption of vagal signaling in the presence of hyperinsulinemia and hyperglycemia resulting from peripheral glucose infusion did not affect NHGU, further supporting our previous suggestion that vagal input to the liver is not a primary determinant of NHGU.