The Effect of the Hepatic Nerves on the Disposition of a Mixed Meal by Conscious Dogs

Abstract

We examined the disposition of a mixed meal by nine conscious dogs fasted for 24 hours with surgical hepatic denervation. The results were compared with those from identical studies carried out previously in 13 hepatic-innervated dogs. Net gut release of glucose and gluconeogenic precursors (assessed with the arteriovenous difference technique), the resulting blood glucose and plasma insulin concentrations, and the hepatic glucose load were remarkably similar in the two groups. Net hepatic glucose uptake was 4.8 +/- 3.6 g in hepatic-denervated and 7.7 +/- 3.3 g in hepatic-innervated dogs. Cumulative net hepatic lactate release in hepatic-denervated dogs was 4.3 +/- 1.4 g of glucose equivalents, half the value for hepatic-innervated dogs. Net hepatic carbon intake was similar in the two groups. Hepatic lipogenesis, oxidation, and net glycogen synthesis were qualitatively similar between groups. In conclusion, the disposition of a mixed meal by hepatic-innervated and hepatic-denervated dogs was very similar. Subtle alterations in net hepatic balance of substrates (tendencies toward decreases in net hepatic glucose uptake and lactate release) made net carbon retention in denervated livers virtually identical with that in innervated livers. When other compensatory mechanisms are intact, hepatic denervation does not significantly alter hepatic disposition of a mixed meal.

Effect of hepatic denervation on peripheral insulin sensitivity in conscious dogs

“…Hepatic blood flow (HBF) was calculated by two methods, ultrasonic flow probes and dye extraction (27). The results obtained with ultrasonic flow probes and ICG were not significantly different.…”

“…The collection, processing, and analysis of blood samples have been described in detail elsewhere (27). At 180 min, the dogs were killed with an overdose of pentobarbital sodium, and tissue was immediately taken from each liver lobe and freezeclamped in liquid nitrogen for analysis of norepinephrine concentration (25).…”

“…Blood glucose, lactate, glycerol, and hematocrit and plasma glucose, insulin, and glucagon concentrations were determined as described previously (27).…”

Evidence against a Physiologic Role for Acute Changes in CNS Insulin Action in the Rapid Regulation of Hepatic Glucose Production

“…In support of these human data, the regulation of hepatic glucose metabolism during the basal state, during hyperinsulinemic clamps and during feeding conditions (ie. mixed meal, oral glucose or intraduodenal glucose challenges) was largely intact in dogs (Moore et al, 1994; Moore et al, 2002; Moore et al, 1993) and rats (Kissler et al, 2005) subjected to complete hepatic denervation.…”

Effects of cyclosporine A and prednisone treatment on mixed meal disposition in dogs with hepatic denervation

“…Dogs with chronic hepatic denervation (DN) displayed a blunting of net hepatic glucose uptake (NHGU) in response to a mixed-meal feeding, although their insulin and arterial blood glucose responses were indistinguishable from those in the normal dogs. 8 In addition, hepatic denervation is associated with insulin resistance in the peripheral tissues. 9,10 On the other hand, when the response to a mixed meal was examined in dogs given CyA (15 mg/kg daily) and prednisone (5 mg twice daily) for 7 days, NHGU was found to be markedly enhanced in comparison to the NHGU in dogs not receiving the medications.…”