Role of glucose in modulating Mg2+ homeostasis in liver cells from starved rats (original) (raw)
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AJP Gastrointestinal and Liver Physiology
␣1-Adrenoceptor-induced Mg 2ϩ extrusion from rat hepatocytes occurs via Na ϩ -dependent transport mechanism. Am J Physiol Gastrointest Liver Physiol 280: G1145-G1156, 2001.-The stimulation of the ␣ 1-adrenergic receptor by phenylephrine results in a sizable extrusion of Mg 2ϩ from liver cells. Phenylephrine-induced Mg 2ϩ extrusion is almost completely abolished by the removal of extracellular Ca 2ϩ or in the presence of SKF-96365, an inhibitor of capacitative Ca 2ϩ entry. In contrast, Mg 2ϩ extrusion is only partially inhibited by the Ca 2ϩchannel blockers verapamil, nifedipine, or (ϩ)BAY-K8644. Furthermore, Mg 2ϩ extrusion is almost completely prevented by TMB-8 (a cell-permeant inhibitor of the inositol trisphosphate receptor), 1,2-bis(2-aminophenoxy)ethane-N,N,NЈ,NЈtetraacetic acid (an intracellular Ca 2ϩ -chelating agent), or W-7 (a calmodulin inhibitor) Thapsigargin can mimic the effect of phenylephrine, and the coaddition of thapsigargin and phenylephrine does not result in an enlarged extrusion of Mg 2ϩ from the hepatocytes. Regardless of the agonist used, Mg 2ϩ extrusion is inhibited by Ͼ90% when hepatocytes are incubated in the presence of physiological Ca 2ϩ but in the absence of extracellular Na ϩ . Together, these data suggest that the stimulation of the hepatic ␣ 1-adrenergic receptor by phenylephrine results in an extrusion of Mg 2ϩ through a Na ϩ -dependent pathway and a Na ϩ -independent pathway, both activated by changes in cellular Ca 2ϩ .
Regulation of Mg2+ homeostasis by insulin in perfused rat livers and isolated hepatocytes
FEBS Letters, 1996
Several recent studies demonstrate that adrenergic supported by evidence revealing that conditions of decreased receptor stimulation evokes marked changes in Mg 2+ homeinsulin release are associated with alterations of blood and ostasis. As insulin counter-regulates many of the metabolic tissue Mg 2÷ level [14,16]. consequences of adrenergic receptor stimulation, we evaluated
Streptozotocin-induced diabetes impairs Mg2+ homeostasis and uptake in rat liver cells
AJP: Endocrinology and Metabolism, 2003
Streptozotocin-induced diabetes impairs Mg 2ϩ homeostasis and uptake in rat liver cells. Am J Physiol Endocrinol Metab 286: E184-E193, 2004; 10.1152/ajpendo.00200.2003.-Male Sprague-Dawley rats rendered diabetic by streptozotocin injection presented 10 and 20% decreases in total hepatic Mg 2ϩ content at 4 and 8 wk, respectively, following diabetes onset. This decrease was associated with a parallel decrease in K ϩ and ATP content and an increase in Na ϩ level. In diabetic liver cells, the Mg 2ϩ extrusion elicited by ␣ 1-adrenoceptor stimulation was markedly reduced compared with nondiabetic livers, whereas that induced by -adrenoceptor stimulation was unaffected. In addition, diabetic hepatocytes did not accumulate Mg 2ϩ following stimulation of protein kinase C pathway by vasopressin, diacylglycerol analogs, or phorbol 12-myristate 13-acetate derivates despite the reduced basal content in cellular Mg 2ϩ . Experiments performed in purified plasma membrane from diabetic livers located the defect at the level of the bidirectional Na ϩ /Mg 2ϩ exchanger operating in the basolateral domain of the hepatocyte cell membrane, which could extrude but not accumulate Mg 2ϩ in exchange for Na ϩ . The impairment of Mg 2ϩ uptake mechanism, in addition to the decrease in cellular ATP level, can contribute to explaining the decrease in liver Mg 2ϩ content observed under diabetic conditions. magnesium; adrenergic signaling; protein kinase c; adenosine 5Јtriphosphate; plasma membrane Address for reprint requests and other correspondence: A. Romani,
Norepinephrine evokes a marked Mg2+ efflux from liver cells
FEBS Letters, 1990
The addition of norepinephrine to perfused rat livers and to collagenase isolated hepatocytes induced a marked and dose-dependent magnesium efflux. The addition of ,Sadrenergic receptor antagonists, but not a-antagonists, completely blocked the Mgl+ e&x. The Mgs+ eflhrx could also be induced by forskolin and by permeable CAMP analogues. By contrast, the addition of carbachol or vasopressin induced a M&' influx into isolated hepatocytes. These results indicate that a significant Mgl+ efflux from liver cells can be induced through the fi-adrenergic receptors and that it is mediated through the cytosolic CAMP levels.
AJP Gastrointestinal and Liver Physiology
Activation of Na ϩ -and Ca 2ϩ -dependent Mg 2ϩ extrusion by ␣ 1 -and -adrenergic agonists in rat liver cells. Am J Physiol Gastrointest Liver Physiol 279: G943-G950, 2000.-The administration of selective ␣ 1 (phenylephrine)-,  (isoproterenol)-, or mixed (epinephrine) adrenergic agonists induces a marked Mg 2ϩ extrusion from perfused rat livers. In the absence of extracellular Ca 2ϩ , phenylephrine does not induce a detectable Mg 2ϩ extrusion, isoproterenol-induced Mg 2ϩ mobilization is unaffected, and epinephrine induces a net Mg 2ϩ extrusion that is lower than in the presence of extracellular Ca 2ϩ and quantitatively similar to that elicited by isoproterenol. In the absence of extracellular Na ϩ , no Mg 2ϩ is extruded from the liver irrespective of the agonist used. Similar results are observed in perfused livers stimulated by glucagon or 8-chloroadenosine 3Ј,5Ј-cyclic monophosphate. In the absence of extracellular Na ϩ or Ca 2ϩ , adrenergic-induced glucose extrusion from the liver is also markedly decreased. Together, these results indicate that liver cells extrude Mg 2ϩ primarily via a Na ϩ -dependent mechanism. This extrusion pathway can be activated by the increase in cellular cAMP that follows the stimulation by glucagon or a specific -adrenergic receptor agonist or, alternatively, by the changes in cellular Ca 2ϩ induced by the stimulation of the ␣ 1 -adrenoceptor. In addition, the stimulation of the ␣ 1 -adrenoceptor appears to activate an auxiliary Ca 2ϩ -dependent Mg 2ϩ extrusion pathway. Finally, our data suggest that experimental conditions that affect Mg 2ϩ mobilization also interfere with glucose extrusion from liver cells.
Metabolism, 2003
Plasma membrane vesicles purified from livers of 4-week-old streptozotocin-injected diabetic rats present an increased basal and cation-stimulated magnesium (Mg) 2؉ transport as compared with vesicles purified from age-matched nondiabetic animals. Furthermore, diabetic basolateral membranes are unable to accumulate extravesicular Mg 2؉ in exchange for intravesicular sodium (Na) ؉ . Loading diabetic vesicles with varying concentrations of D-glucose, in addition to Mg 2؉ , renormalizes basal and Na ؉ -or calcium (Ca) 2؉ -induced Mg 2؉ extrusion in a dose-dependent manner, but does not restore Na ؉ /Mg 2؉ exchanger reversibility. A similar effect on Mg 2؉ extrusion is observed when D-glucose is replaced with 2-deoxyglucose, amylopectin, or glycogen. The loading with 3-methyl-O-glucose or L-glucose, instead, affects basal and Na ؉dependent Mg 2؉ extrusion, but not Ca 2؉ -dependent Mg 2؉ fluxes. In contrast, loading the vesicles with hexoses other than glucose or varying extravesicular glucose concentration from 5 to 20 mmol/L does not modify basal or cation-stimulated Mg 2؉ fluxes. Taken together, these data indicate that basal and cation-stimulated Mg 2؉ transport across the hepatocyte plasma membrane is altered under diabetic conditions as a result of a decrease in intravesicular (intracellular) glucose.
Low Hepatic Mg2+ Content promotes Liver dysmetabolism: Implications for the Metabolic Syndrome
Journal of Metabolic Syndrome, 2014
Metabolic Syndrome, a pathological condition affecting approximately 35% of the USA population, is characterized by obesity, insulin resistance, and hypertension. Metabolic syndrome is considered the single most common condition predisposing to the development of various chronic diseases including diabetes and hypertension. Hypomagnesaemia has been consistently observed in association with metabolic syndrome, but it is unclear whether reduced Mg 2+ levels are the consequence or a possible cause for the development of the metabolic syndrome and/or its associated pathologies.