Effects Of Hepatic Vagotomy Research Articles

Hepatocyte proliferation in rats after ventromedial hypothalamic lesions: immunoreactivity patterns of proliferating cell nuclear antigen (PCNA).

Ventromedial hypothalamic (VMH) lesions result in increased DNA content in the rat liver. However, little information is available concerning the proliferative activity and lobular distribution of different cell populations in VMH-lesioned rat liver. The aim of the present study was to quantitatively assess these parameters in VMH-lesioned rat liver by measuring proliferating cell nuclear antigen (PCNA) reactivity. We investigated to determine whether this mitotic response involves acinar zones 1, 2, or 3. Changes in immunohistochemical labeling indices in rat liver were measured with an antibody against PCNA until 7 days after VMH lesioning. The effects of hepatic vagotomy on proliferation were also examined. Proliferation of hepatocytes in acinar zones 1-3 began to increase on day 1, and reached a maximum at 3 days. The area of most intense proliferation progressively shifted from acinar zone 1 to zone 3 in several days. The proliferation was completely inhibited by hepatic vagotomy, indicating that VMH lesions induce cell proliferation in rat liver via hepatic vagus nerve activity. This study implicates the information available on neural factors which initiate hepatocyte proliferation.

Effect of hepatic vagotomy on plasma insulin levels during fasting in rats

The present investigation was designed to evaluate the effect of a selective hepatic vagotomy (HV) on the insulin response in rats fasted for 24 h when blood glucose levels were or were not maintained by a constant glucose infusion. Rats were divided into three dietary groups: one group of normally fed rats, one group of 24-h fasted rats, and one group of 24-h fasted rats infused with glucose throughout the fasting period. Each one of these groups was subdivided into HV and sham-operated (SHM) rats. Fasting without glucose infusion resulted in a significant ( p < 0.05) decrease in plasma glucose, liver glycogen, and insulin concentrations and in a significant ( p < 0.05) increase in β-hydroxybutyrate and FFA concentrations. Despite the maintenance of plasma glucose concentrations in the glucose-infused groups, the concentrations of liver glycogen and insulin were still decreased ( p < 0.01) and the concentrations of β-hydroxybutyrate were still increased ( p < 0.05) at the end of the fasting period. However, no significant differences in insulin or in β-hydroxybutyrate concentrations were found between HV and SHM rats. It is concluded that the decline in plasma glucose concentration during fasting does not totally explain the insulinopenic response to fasting, and that the liver, through the mediation of the hepatic vagus nerve does not seem to contribute to insulinopenia in 24-h fasted rats.

Effect of hepatic vagotomy on plasma catecholamines during exercise-induced hypoglycemia.

The existence of a hepatosympathetic reflex active during insulin-induced hypoglycemia has recently been reported. The purpose of the present investigation was to test the hypothesis that the liver, through the afferent innervation of the vagus nerve, contributes to plasma epinephrine and norepinephrine responses during exercise-induced hypoglycemia. Hepatic vagotomized and sham-operated rats were killed at rest or after 30, 60, and 120 min of running exercise (26 m/min, 0% grade). At the end of the 120-min exercise period, liver glycogen, glucose, and insulin levels measured in the portal and peripheral plasma were all significantly reduced (P < 0.05) while epinephrine and norepinephrine concentrations, beta-hydroxybutyrate, lactate, and portal and peripheral glucagon plasma levels were all significantly increased (P < 0.05). However, no significant differences were observed between hepatic vagotomized and sham-operated rats at rest and after exercise for the metabolic and hormonal responses. These results suggest that if a hepatosympathetic reflex is active during an exercise-induced hypoglycemia situation, then this contribution is probably hidden by more important regulatory mechanisms.

Hepatic vagal amino acid sensors modulate amino acid induced insulin and glucagon secretion in the rat

To clarify the physiological role of vagal amino acid sensors in the liver, the effect of hepatic vagotomy and/or celiac vagotomy (sectioning of the hepatic branch and/or celiac branches of the vagus nerve) on the secretion of insulin and glucagon after intraperitoneal injection of neutral ( l-alanine, l-leucine, and l-phenylalanine), acidic ( l-glutamate), or nonmetabolized (cycloleucine) acids, was examined in rats. Hepatic vagotomy enhanced both plasma glucose and glucagon concentrations after intraperitoneal injection of alanine more than those in sham-vagotomized (control) rats, while after intraperitoneal injection of leucine, hepatic vagotomy decreased plasma glucose concentrations and enhanced plasma insulin concentrations more than in control animals. These effects, following both alanine and leucine administration, were blocked by celiac vagotomy. Glutamate, phenylalanine, and cycloleucine stimulation in hepatic-vagotomized rats caused no significant differences in plasma glucose, insulin, or glucagon levels as compared to those in sham-vagotomized rats. Celiac vagotomy alone did not affect plasma glucose, insulin, or glucagon concentrations after stimulation by these five amino acids. The physiological role of alanine and leucine sensors may be to prevent amino acid-induced exaggerated pancreatic hormone secretion and to maintain blood glucose homeostasis, while glutamate, phenylalanine, and cycloleucine have no effect on this pancreatic neuroendocrine system.

Effects of hepatic vagotomy on suppression of water intake during portal infusion of water by water deprived rats

Effects of hepatic vagotomy on suppression of water intake during portal infusion of water by water deprived rats

Effect of hepatic vagotomy on hormonal response to exercise in gluconeogenesis-inhibited rats

The liver, through the afferent pathway of the hepatic vagus nerve, has been reported to influence the hormonal response to exercise in adrenodemedullated rats. The present investigation was designed to evaluate the role played by gluconeogenesis in this hepatic influence. To this end, we studied the effects of a selective hepatic vagotomy on the hormonal response to a 30-min treadmill run (26 m/min, 0% grade) in adrenodemedullated rats injected with 3-mercaptopicolinic acid, a gluconeogenic inhibitor. Hepatic vagotomy was associated with small but significant higher (P less than 0.05) elevations of peripheral blood glucose levels at rest and after exercise. No significant differences were observed between hepatic-vagotomized and sham-operated rats in either resting or exercising levels of liver glycogen, portal glucose, portal and peripheral insulin and glucagon, and peripheral epinephrine and norepinephrine. All hormonal responses, with the exception of epinephrine, were either decreased or increased similarly in the two experimental conditions after exercise. These data indicate that contrary to what has been reported in rats with an intact capacity for gluconeogenesis, hepatic-vagotomized and sham-operated rats with an inhibited gluconeogenesis had similar hormonal responses to exercise. It is concluded that gluconeogenesis plays a role in the afferent neural influence exerted by the liver via the hepatic vagus nerve in the regulation of hormonal response to exercise.

Modulation of Arginine-Induced Insulin and Glucagon Secretion by the Hepatic Vagus Nerve in the Rat: Effects of Celiac Vagotomy and Administration of Atropine

We hypothesized the existence of vagal arginine sensors in the liver which modulate arginine-induced pancreatic hormone secretion. The present study was carried out to examine the efferent pathways and receptor mechanisms from arginine sensors using selective vagotomies and autonomic drugs on the secretion of insulin and glucagon after ip injection of L-arginine (1 g/kg BW) in rats in an unanesthetized and unrestrained state. Hepatic vagotomy (sectioning of the hepatic branch of the vagus nerve) enhanced both plasma insulin and glucagon concentrations after ip arginine more than those in sham-vagotomized (control) rats. The effect of hepatic vagotomy was blocked by adding celiac vagotomy (sectioning of the celiac branches of the vagus nerve) or by previous administration of atropine methyl nitrate (10 mg/kg BW), but not by phentolamine (1 mg/kg BW) or propranolol (2 mg/kg BW). Celiac vagotomy alone did not affect the plasma insulin concentration; however, it reduced the plasma glucagon concentration after ip arginine compared to that in sham-vagotomized rats. Administration of atropine alone did not affect plasma insulin or glucagon concentrations after ip arginine. These results suggest that celiac branches of the vagus nerve act as efferent pathways to the pancreas through a muscarinic receptor mechanism in the hepatic arginine sensor-mediated pancreatic neuroendocrine system. The physiological role of these hepatic sensors may be to prevent arginine-induced exaggerated pancreatic hormone secretion and maintain blood glucose homeostasis.

Hepatic Vagotomy Abolishes the Circadian Rhythm of Lipogenic Responsiveness to Insulin and Reduces Fat Stores in Hamsters

The effects of hepatic vagotomy upon the circadian rhythm of lipogenesis and body fat store levels were tested in seasonally obese Syrian hamsters. Lipogenesis was studied 8 weeks after surgery by measuring the incorporation of label into epididymal and retroperitoneal fat pad lipid in animals killed 30 min after intraperitoneal [3H]-glucose injection and 2 h after bovine insulin injections. A marked circadian variation in insulin-stimulated lipogenesis was present in sham-operated controls. The peak of lipogenic activity occurred at light onset and was 3-fold greater than during the middle of the photophase. The peak in the circadian variation of plasma insulin coincided with the peak of lipogenic responsiveness to insulin in these animals. Hepatic vagotomy completely abolished the circadian variation in insulin-stimulated lipogenesis and reduced the magnitude of the daily lipogenic peak at light onset by 65%, but only slightly altered the phase of the circadian variation in plasma insulin by 4 h. Hepatic vagotomy did not influence plasma glucose levels, which did not vary as a function of time of day in either group. Body fat stores were severely reduced (40%) by hepatic vagotomy when examined 8 weeks after surgery. The present study demonstrates important roles for interactions of the circadian rhythms of insulin and tissue lipogenic responses to insulin in the regulation of body fat stores. Furthermore, this study demonstrates that hepatic vagal activity regulates the daily interval of lipogenic responsiveness to insulin and thereby directly influences body fat stores in the Syrian hamster.

Hepatic vagotomy increases consumption of a novel-tasting diet presented immediately after surgery

To further characterize the possible effect of hepatic vagotomy on food intake, rats adapted to a medium-fat diet (MF diet) were offered a novel-tasting diet immediately after hepatic branch vagotomy (HBX rats) or sham vagotomy (SHAM rats) and food intake as well as diet selection (novel-tasting vs. familiar diet) was measured. When a novel-tasting sweet medium-fat diet (SMF diet) was offered immediately after surgery, HBX rats are transiently more (days 1–4 after surgery) and selected more (days 5 and 6 after surgery) of the SMF diet than SHAM rats. Similar results were obtained when a novel-tasting bitter diet (AMF diet) was offered instead of the SMF diet. In contrast, when rats adapted to the AMF diet prior to surgery were given normal MF diet as novel-tasting diet immediately after surgery, HBX and SHAM rats' postoperative food intake and diet selection did not differ. When rats were given only MF or SMF diet before and after surgery, HBX and SHAM rats' food intake during the initial postoperative period also did not differ. The results indicate that hepatic branch vagotomy and sham vagotomy have different aversive effects which lead to transient differences in postoperative food intake when diets with a novel and strong taste are presented during the initial postoperative period. Therefore, information conveyed by the hepatic branch of the vagus can apparently lead to a conditioned feeding response. This is evidence for a more subtle role of the liver in the control of food intake than previously thought.

Effect of hepatic vagotomy on postexercise substrate levels in food-restricted rats.

The metabolic effects of a selective hepatic vagotomy (HV) were investigated at rest and immediately after a 50-min exercise period (26 m/min, 0% grade) in rats subjected to an overnight 50% food restriction. This dietary restriction reduced liver glycogen content to 50% of normal resting concentrations (2.2-2.8 g/100 g). No significant differences between HV and sham-operated rats were found in resting and exercising beta-hydroxybutyrate, glucose, glycerol, and insulin concentrations. Postexercise liver glycogen concentrations were reduced to approximately 1.0 g/100 g in both HV and sham-operated groups. This decrease was associated with significantly (P less than 0.01) lower postexercise glycogen levels in the soleus muscle of HV rats (2.6 times) along with higher plasma free fatty acid concentrations (P less than 0.01). These data provide evidence that HV combined with a progressive decrease in liver glycogen content may influence substrate regulation during exercise. They also support the concept of the existence of hepatic glucoreceptors responsive to a decrease in liver glycogen content.

Role of the hepatic branch of the vagus nerve in liver regeneration in rats

The role of the vagus nerve in liver regeneration after partial hepatectomy was examined by comparing the effects of hepatic vagotomy (sectioning of the hepatic branch of the vagus nerve) with those of subdiaphragmatic vagotomy in rats. Hepatic vagotomy delayed but did not suppress the increase in the rate of hepatic DNA synthesis and the activity of thymidine kinase after partial hepatectomy. On the other hand, subdiaphragmatic vagotomy delayed and suppressed these indices. The time courses of restoration of liver DNA content after partial hepatectomy were not affected by hepatic vagotomy. However, this index was both delayed and suppressed in subdiaphragmatic vagotomized rats. Hepatic vagotomy did not affect the daily food intake or the body weight increase after partial hepatectomy. However, subdiaphragmatic vagotomy caused considerably more loss of food intake and body weight. There were no differences in the plasma insulin levels after partial hepatectomy among three groups. We concluded that a vagal specific effect is evident in the delay but fails to suppress liver regeneration.

Effect of hepatic vagotomy and/or coeliac ganglionectomy on the delayed eating response to insulin and 2DG injection in rats

The eating response that occurs following recovery from the effects of insulin or 2-deoxy-D-glucose (2DG) injection was examined in rats with hepatic vagotomy and/or coeliac ganglionectomy. Rats were deprived of food and injected with either saline (1 ml/kg), regular insulin (3 U/kg) or 2DG (200 mg/kg). Plasma glucose was measured periodically over the next 6 hr and then food was returned and intakes were measured over the next 2 hr. Rats increased food intake 6–8 hr after insulin or 2DG injection compared to the saline (control) condition. Nerve section did not affect the plasma glucose or food intake responses to insulin or 2DG injection. The results indicate that the innervation of the liver via the vagus nerve or coeliac ganglion is not involved in the delayed eating response to insulin and 2DG injection.