Evaluation of selective liver denervation methods

Cucchiaro, Giovanni; Yamaguchi, Yasuo; Mills, E; Kuhn, Cynthia M.; Anthony, Douglas C.; Branum, Gene D.; Epstein, Robert E.; Meyers, William C.

doi:10.1152/ajpgi.1990.259.5.g781

Cited by 23 publications

(26 citation statements)

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“…These studies in general have focused on the liver as the source of the afferent signal, rather than the portal vein. Two studies that used complete liver denervation by surgical stripping or cutting found no effect on counterregulation during insulin-induced hypoglycemia (17,26). In contrast, an investigation in which the liver was denervated by the application of phenol to the hepatic vasculature yielded similar findings to the current investigation (28).…”

Section: Discussionmentioning

confidence: 99%

“…Phenol (90% wt/vol) was applied to a 1.5-cm region of the portal vein proximal to the liver. Portal vein extravascular tissue necrosis, denoted by vessel discoloration, was observed in all phenol-treated animals (17). The same physical procedure was performed on the remaining control animals (shamoperated group [SHAM]) with the exception that 0.9% NaCl was substituted for 90% phenol.…”

Section: Methodsmentioning

confidence: 99%

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Portal vein afferents are critical for the sympathoadrenal response to hypoglycemia.

2000

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We sought to elucidate the role of the portal vein a fferents in the sympathetic response to hypoglycemia. Laparotomy was performed on 27 male Wi s t a r rats. Portal veins were painted with either 90% phenol (denervation group [PDN]) or 0.9% saline solution (sham-operated group [SHAM]). Rats were chronically cannulated in the carotid artery (sampling), jugular vein (infusion), and portal vein (infusion). After a recovery period of 5 days, animals were exposed to a hyperinsulinemic-hypoglycemic clamp, with glucose infused either portally (POR) or peripherally (PER). In all animals, systemic hypoglycemia (2.48 ± 0 . 0 9 mmol/l) was induced via jugular vein insulin infusion (50 mU · k g -1 · min -1 ). Arterial plasma catecholamines were assessed at basal (-30 and 0 m i n ) and during sustained hypoglycemia (60, 75, 90, and 105 min). By design, portal vein glucose concentrations were significantly elevated during POR versus PER (4.4 ± 0.14 vs. 2.5 ± 0.07 mmol/l; P < 0.01, respectively) for both PDN and SHAM. There were no significant differences in arterial glucose or insulin concentration between the four experimental conditions at any point in time. When portal glycemia and systemic glycemia fell concomitantly (SHAM-PER), epinephrine increased 12-fold above basal (3.75 ± 0.34 and 44.56 ± 6.1 nmol/l; P < 0.001). However, maintenance of portal normoglycemia (SHAM-POR) caused a 50% suppression of the epinephrine response, despite cerebral hypoglycemia (22.2 ± 3.1 nmol/l, P < 0.001). Portal denervation resulted in a significant blunting of the sympathoadrenal response to whole-body hypoglycemia (PDN-PER 27.6 ± 3.8 nmol/l vs. SHAM-PER; P < 0.002). In contrast to the sham experiments, there was no further suppression in arterial epinephrine concentrations observed during PDN-POR versus PDN-PER (P = 0.8). These findings indicate that portal vein afferent innervation is critical for hypoglycemic detection and normal sympathoadrenal counterregulation. D i a b e t e s 4 9 :8-12, 2000 C atecholamines constitute the primary defense against hypoglycemia for individuals with type 1 diabetes, in which the ability to suppress insulin is absent and the capacity to secrete glucagon is diminished. The catecholamine response has been well characterized for both normal and diabetic individuals (1-4). Under normal conditions, this sympathetic response appears sufficient to compensate for the loss of other counterregulatory measures (1,2). Unfortunately, over time, the catecholamine response for individuals with type 1 diabetes diminishes relative to the fall in blood glucose (1,2). The diminished catecholamine response appears to have been further exacerbated by increasingly aggressive attempts to control blood glucose levels in type 1 diabetic patients (3,4).Although iatrogenic hypoglycemia has been invoked as a partial explanation, in general, the pathology of the diminished sympathetic response in patients with type 1 diabetes remains poorly understood. In part, this can be attributed to the lack of knowledge concerning the locus f...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Portal vein afferents are critical for the sympathoadrenal response to hypoglycemia.

2000

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“…Care was taken not to disrupt the occipital, cranial, laryngeal, or other arterial branches in close proximity. To assure disruption of all neural tissue, the skeletonized areas were swabbed with alcohol (13). After the closure of the incision sites, the effectiveness of carotid body removal was verified by the absence of a ventilatory response to NaCN (20-40 µg/kg).…”

Section: Y Koyama and Associatesmentioning

confidence: 99%

Evidence that carotid bodies play an important role in glucoregulation in vivo.

et al. 2000

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The carotid bodies are sensitive to glucose in vitro and can be stimulated to cause hyperglycemia in vivo. The aim of this study was to determine if the carotid bodies are involved in basal glucoregulation or the counterregulatory response to an insulin-induced decrement in arterial glucose in vivo. Dogs were surgically prepared >16 days before the experiment. The carotid bodies and their associated nerves were removed (carotid body resected [CBR]) or left intact (Sham), and infusion and sampling catheters were implanted. Removal of carotid bodies was verified by the absence of a ventilatory response to NaCN. Experiments were performed in 18-h fasted conscious dogs and consisted of a tracer ([3-3 H]glucose) equilibration period (-120 to -40 min), a basal period (-40 to 0 min), and an insulin infusion (1 mU · kg -1 · min -1 ) period (0-150 min) during which glucose was infused as needed to clamp at mildly hypoglycemic (65 mg/dl) or euglycemic (105 mg/dl) levels. Basal (8 µU/ml) and clamp (40 µU/ml) insulin levels were similar in both groups. Basal arterial glucagon was reduced in CBR compared with Sham (30 ± 2 vs. 40 ± 2 pg/ml) and remained reduced in CBR during hypoglycemia (peak levels of 36 ± 3 vs. 52 ± 7 pg/ml). Cortisol levels were not significantly different between the 2 groups in the basal state, but were reduced during the hypoglycemic clamp in CBR. Catecholamine levels were not significantly different between the 2 groups in the basal and hypoglycemic periods. The glucose infusion rate required to clamp glucose at 65 mg/dl was 2.5-fold greater in CBR compared with Sham T here is considerable uncertainty as to the site at which decrements in blood glucose are sensed. Sites in the brain (1), portal vein (2,3), liver (4), and pancreas (5) are all sensitive to blood glucose. Despite intensive investigation, however, the physiological role of these glucose-sensitive regions are highly controversial because no one site can completely explain the full counterregulatory response to hypoglycemia.We tested the hypothesis that the carotid bodies (or receptors near this site) are instrumental in detecting a decrement in blood glucose. This hypothesis was based on evidence that 1) the carotid bodies can detect glucose (6-8), 2) the carotid bodies have the "circuitry" to provide input to centers involved in glucoregulation (7-10), and 3) the carotid bodies have unique physiological characteristics making them potentially highly sensitive to changes in blood glucose content (high blood flow and metabolic rate per gram tissue) (11).To examine the role of the carotid bodies (or receptors anatomically near them), carotid body resected (CBR) conscious dogs or dogs having undergone a sham surgery (Sham) were studied in the basal state and during hyperinsulinemic, euglycemic, or hypoglycemic clamps. Isotope dilution methods were used to calculate glucose kinetics. RESEARCH DESIGN AND METHODSAnimal maintenance and surgical procedures. Mongrel dogs (n = 23, mean weight 25.1 ± 0.6 kg) of either sex that had been fed a standard...

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“…A method similar to that described by Cucchiaro et al 21 was adopted. Briefly, after anaesthesia and laparotomy, the hepatic ligaments were loosened and the portal vein, common duct and hepatic artery were dissected.…”

Section: Denervation Protocolmentioning

confidence: 99%

Hepatic denervation impairs the assembly and secretion of VLDL‐TAG

Tavares

Seelaender

2008

Cell Biochemistry & Function

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VLDL secretion is a regulated process that depends on the availability of lipids, apoB and MTP. Our aim was to investigate the effect of liver denervation upon the secretion of VLDL and the expression of proteins involved in this process. Denervation was achieved by applying a 85% phenol solution onto the portal tract, while control animals were treated with 9% NaCl. VLDL secretion was evaluated by the Tyloxapol method. The hepatic concentration of TAG and cholesterol, and the plasma concentration of TAG, cholesterol, VLDL-TAG, VLDL-cholesterol and HDL-cholesterol were measured, as well as mRNA expression of proteins involved in the process of VLDL assembly. Hepatic acinar distribution of MTP and apoB was evaluated by immunohistochemistry. Denervation increased plasma concentration of cholesterol (125.3 +/- 10.1 vs. 67.1 +/- 4.9 mg dL(-1)) and VLDL-cholesterol (61.6 +/- 5.6 vs. 29.4 +/- 3.3 mg dL(-1)), but HDL-cholesterol was unchanged (45.5 +/- 6.1 vs. 36.9 +/- 3.9 mg dL(-1)). Secretion of VLDL-TAG (47.5 +/- 23.8 vs. 148.5 +/- 27.4 mg dL h(-1)) and mRNA expression of CPT I and apoB were reduced (p < 0.01) in the denervated animals. MTP and apoB acinar distribution was not altered in the denervated animals, but the intensity of the reaction was reduced in relation to controls.

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Evaluation of selective liver denervation methods

Cited by 23 publications

References 0 publications

Portal vein afferents are critical for the sympathoadrenal response to hypoglycemia.

Portal vein afferents are critical for the sympathoadrenal response to hypoglycemia.

Evidence that carotid bodies play an important role in glucoregulation in vivo.

Hepatic denervation impairs the assembly and secretion of VLDL‐TAG

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