Intracellular mechanism of action of sympathetic hepatic nerves on glucose and lactate balance in perfused rat liver

Balle, C.; Beuers, Ulrich; Engelhardt, Regina; Jungermann, Kurt

doi:10.1111/j.1432-1033.1987.tb13686.x

Cited by 19 publications

(17 citation statements)

References 55 publications

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“…In calcium-free perfusions, nerve-stimulation-dependent metabolic alterations occurred with normal kinetics when calcium was added 3 min prior to stimulation; they were, however, delayed when calcium was added only 2 min after the onset of stimulation. This indicated that calcium release from intracellular pools was involved in the signal chain [96] (Fig. 9).…”

Section: Metabolismmentioning

confidence: 86%

“…The level of the activators of glycogenolysis (CAMP) and glycolysis (fructose-2,6-bisphosphate), increased slightly [96]. The slight increase in CAMP could not account for the increase in glycogen phosphorylase activity.…”

Section: Metabolismmentioning

confidence: 94%

“…6) [98]. In the 'calcium deprivation/replenishment' experiments, the nerve-stimulation-mediated flow reduction was restored immediately after readdition of calcium [96]. Thus, the hemodynamic nerve effects were dependent on the entry of extracellular calcium into the smooth muscle cells.…”

Section: Metabolismmentioning

confidence: 96%

“…3). The release of noradrenaline from the nerve endings and thus the noradrenaline overflow and all effects of electrical-nerve stimulation are strictly dependent on the presence of extracellular calcium [73,96,971. …”

Section: Noradrenaline Releasementioning

confidence: 99%

“…The possible involvement of intracellular calcium in the 'metabolic' signal chain of events was tested in 'calcium deprivation/replenishment' experiments [96]. The idea was that intracellular calcium pools should be emptied during a prolonged calcium-free perfusion and, thus, processes depending on intracellular calcium should be inhibited.…”

Section: Metabolismmentioning

confidence: 99%

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Nervous control of liver metabolism and hemodynamics

Gardemann

Püschel

Jungermann

1992

European Journal of Biochemistry

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100

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Besides being a center of intermediary metabolism, a center of defense and a control center for the hormonal system, the liver acts as the glucose reservoir of the organism and, moreover, as an important blood reservoir, by taking up or releasing glucose and blood. The many diverse hepatic functions are controlled by the substrate concentrations in blood, the circulating hormone levels, the biomatrix and the autonomic hepatic nerves. In this review, the present knowledge on the metabolic and hemodynamic effects, the mechanism of action and the function of the hepatic nerves, as studied in the isolated perfused liver, are summarized. Effects of hepatic nerve stimulationIn perfused rat liver, activation of the sympathetic liver nervesincreases glucose and lactate release, urate and allantoin formation, decreases ketogenesis, urea release, ammonia uptake, xenobiotics conjugation, bile flow and bile acid secretion as well as oxygen utilization, and causes an overflow of noradrenaline into the hepatic vein. Furthermore, sympathetic stimulation decreases the flow and elicits an intrahepatic redistribution as well as a mobilization of blood by the closing of sinusoids. Activation of parasympathetic nerves enhances glucose utilization and causes re-opening of previously closed sinusoids. The actions of hepatic nerves are modulated by the hormones glucagon, insulin, adrenaline, noradrenaline, vasopressin and angiotensin. Extrahepatocellular signal chain of sympathetic nerve stimulationThe release of noradrenaline from the nerve endings and all effects of electrical nerve stimulation are strictly dependent on the presence of extracellular calcium. Sympathetic nerves regulate the hepatic metabolism of carbohydrates and ketone bodies and the conjugation of xenobiotics directly via interaction with non-parenchymal and parenchymal liver cells. However, sympathetic nerves regulate metabolism of nitrogenous compounds indirectly via reduction of blood flow. Studies with adrenergic and prostanoid agonists and antagonists support the following mechanism. Noradrenaline, released from the nerve endings via al-adrenergic receptors, directly interacts with periportal hepatocytes and also stimulates prostanoid formation in nearby non-parenchymal liver cells. Prostanoids, in turn, modulate metabolism in parenchymal cells. About 50% of the metabolic nerve effects in rat liver are mediated via signal propagation through gap junctions. By this mechanism, rat liver apparently compensates the scarce innervation of only a few parenchymal and non-parenchymal cells in the proximal periportal zone.

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Section: Metabolismmentioning

confidence: 86%

Section: Metabolismmentioning

confidence: 94%

Section: Metabolismmentioning

confidence: 96%

Section: Noradrenaline Releasementioning

confidence: 99%

Section: Metabolismmentioning

confidence: 99%

See 3 more Smart Citations

Nervous control of liver metabolism and hemodynamics

Gardemann

Püschel

Jungermann

1992

European Journal of Biochemistry

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100

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Control of hepatocyte metabolism by sympathetic and parasympathetic hepatic nerves

Püschel

2004

Anat. Rec.

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More than any other organ, the liver contributes to maintaining metabolic equilibrium of the body, most importantly of glucose homeostasis. It can store or release large quantities of glucose according to changing demands. This homeostasis is controlled by circulating hormones and direct innervation of the liver by autonomous hepatic nerves. Sympathetic hepatic nerves can increase hepatic glucose output; they appear, however, to contribute little to the stimulation of hepatic glucose output under physiological conditions. Parasympathetic hepatic nerves potentiate the insulindependent hepatic glucose extraction when a portal glucose sensor detects prandial glucose delivery from the gut. In addition, they might coordinate the hepatic and extrahepatic glucose utilization to prevent hypoglycemia and, at the same time, warrant efficient disposal of excess glucose. Key words: glucose homeostasis; metabolic regulation; insulin sensitivityMore than any other organ, the liver contributes to the maintenance of the metabolic equilibrium of our body. Depending on the nutrient supply, it can shift from net glucose uptake and storage to net glucose output, thereby providing the energy source for those tissues that obligatorily depend on glucose. Liver also is a center of amino acid metabolism and ammonia detoxification, being unique in harboring the complete urea cycle. The rate of hepatic amino acid metabolization and urea formation varies widely, depending on the nutritional state. Besides the gut, the liver is the only organ that contains significant amounts of xanthinoxidase and thus can catalyze the last steps in purine catabolism. Liver is a key player in lipid metabolism, as it synthesizes and degrades lipoproteins and converts fatty acids to ketone bodies. In rodents but not normally in humans, it also synthesizes fatty acids from carbohydrates. Liver is an exocrine gland producing bile acids and it is the only significant site of cholesterol excretion. It is also the prime site of xenobiotic metabolism, chiefly allowing xenobiotic detoxification but also toxification. Finally, it is a control station of the hormone system; different hormones that control the intermediary metabolism are either degraded, activated, or synthesized in the liver. The metabolic pathways serving all these functions are tightly regulated and are subject to control by metabolite levels, circulating hormones, and hepatic nerves. The different levels of control are interrelated in many ways. This complex mode of regulation makes it difficult to discern the contribution of one particular branch of this control system. The role of hepatic nerves in the control of hepatic metabolism has often been disputed because no gross aberration of the metabolic homeostasis was observed when the nervous supply to the liver was interrupted by surgical or pharmacological means. However, although direct nervous control apparently contributes only subtle changes to the metabolic control in liver, it becomes increasingly evident that this fine tuning may ...

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Modulation of Basal Hepatic Glycogenolysis by Nitric Oxide

et al. 1996

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Glycogenolysis is catalysed by glycogen phosphorylactivation of phosphorylase. The NO effect was not addi-ase, an enzyme that exists in two interconvertible tive to maximal stimulation of glycogenolysis (7.7 { 0.2 forms, the active phosphorylated a-form and the inac- strictly depends on covalent activation of phosphoryl-The requirement for activation of phosphorylase was also evidenced by the ineffectiveness of NO in phosphor-ase, 1 by a specific phosphorylase kinase. The kinase is ylase-kinase-deficient livers of gsd/gsd rats. The NO activated by cyclic adenosine monophosphate (cAMP)-effect was blocked by co-administration of cyclooxy-dependent protein kinase, or by direct interaction of genase inhibitors (50 mmol/L ibuprofen, 50 mmol/L in-Ca 2/ with a calmodulin subunit. Ultimately, the catadomethacin, or 2 mmol/L aspirin), suggesting a media-lytic expression of phosphorylase a is under substrate tory role of prostanoids from nonparenchymal cells. control, 2 because cytosolic levels of inorganic phosphate This conclusion was confirmed by the fact that NO did (P i ) fail to saturate substrate demands of activated not activate phosphorylase in isolated hepatocytes. phosphorylase a. Moreover, NO was no longer glycogenolytic in liversControl of hepatic glycogenolysis involves intricate 3-7 Evidence has accumulated inhibited the basal glucose production. This coincided that prostanoids are engaged in the control of glycogenwith an increased elution of cyclic guanosine mono-olysis in liver. Although endotoxin, 8 platelet-activating phosphate (cGMP). Inhibition of glycogenolysis by NO factor, 9 and phorbol esters 3,8 stimulate glycogenolysis under these conditions was blocked by 1 mmol/L the-in intact liver, these compounds are ineffective when ophylline, suggestive for involvement of cGMP-stimu-tested directly on isolated hepatocytes. In the intact lated cAMP phosphodiesterase. However, we could not liver, cyclooxygenase inhibitors suppress stimulation confirm that an increase in cGMP resulted in a drop of prostanoid synthesis and activation of phosphorylase in cAMP. In conclusion, NO recruits opposing mechaby the former agents.10-12 Prostanoids may be directly involved in covalent activation of hepatocellular phosphorylase. 8,13 Indirectly, eicosanoids may trigger vaso- lytic response to platelet-activating factor is sup-

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Intracellular mechanism of action of sympathetic hepatic nerves on glucose and lactate balance in perfused rat liver

Cited by 19 publications

References 55 publications

Nervous control of liver metabolism and hemodynamics

Nervous control of liver metabolism and hemodynamics

Control of hepatocyte metabolism by sympathetic and parasympathetic hepatic nerves

Modulation of Basal Hepatic Glycogenolysis by Nitric Oxide

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