Nervous control of liver metabolism and hemodynamics

Abstract

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.

Defective propagation of signals generated by sympathetic nerve stimulation in the liver of connexin32-deficient mice.

“…Our results strongly support the hypothesis that gap junctions in murine liver mediate intercellular parenchymal propagation of signals received by a subset of hepatocytes from sympathetic nerve endings, presumably through the release of noradrenaline via al-receptors (8). It had been found before in perfused rat liver that activation of sympathetic liver nerves stimulated glucose release, among other alterations of liver metabolism, and decreased the hepatic flow rate (cf.…”

“…Among the hypothetical functions are growth control, metabolic coupling (i.e., exchange of nutrients), and coordination of metabolic activities (1)(2)(3)(4). The latter function in parenchymal tissues is thought to regulate secretion of digestive enzymes in pancreas (5) and release of glucose from glycogen stores in liver (4,(6)(7)(8).…”

A new role for enteric glucagon‐37: acute stimulation of glucose absorption in rat small intestine

“…The operation followed the procedures described before for the joint perfusion of the isolated intestine and liver [10,11] with the exception that the liver was not included in the present experiments. In brief, rats (300-350 g) were anaesthetised by intraperitoneal injection of pentobarbital (60 mg/kg).…”

Decreased S100B expression in chronic liver diseases

“…The hepatic nerve is involved in hemodynamics, bile flow regulation, as well as in carbohydrate and lipid metabolism [3,4]. Activation of the sympathetic nerves increases glucose and lactate release, bile flow, and bile acid secretion [5], and sympathetic nervous overactivity is related to the severity of cirrhosis [3]. …”