Intracellular magnesium and insulin resistance.

Magnesium, the second most abundant intracellular divalent cation, is a cofactor of many enzymes involved in glucose metabolism. Magnesium has an important role in insulin action, and insulin stimulates magnesium uptake in insulin-sensitive tissues. Impaired biological responses to insulin is referred to as insulin resistance. This review was designed to reach a better understanding of the mechanism involved in the correlation between magnesium and insulin resistance. Intracellular magnesium concentration is low in type 2 diabetes mellitus and in hypertensive patients. In patients with type 2 diabetes an inverse association exists between the plasma magnesium and insulin resistance due to intracellular changes. The suppressed intracellular magnesium concentration may result in defective tyrosine kinase activity and modify insulin sensitivity by influencing receptor activity after binding or by influencing intracellular signaling and processing. Intracellular magnesium deficiency may affect the development of insulin resistance and alter the glucose entry into the cell. CONCLUSIONS: Magnesium is required for both proper glucose utilization and insulin signaling. Metabolic alterations in cellular magnesium, which may play the role of a second messenger for insulin action, contribute to insulin resistance.     

镁离子与冠心病关系的研究进展

镁离子(Mg2+)为细胞内含量最多的二价阳离子.人体内Mg2+的主要来源为饮食摄人,主要经回肠吸收,肾脏为其重要排泄器官.机体中Mg2+浓度受多种因素调节,如甲状旁腺激素、降钙素、去甲肾上腺素和肾上腺素等多种激素都影响镁的转运.近年来研究发现细胞膜上瞬时受体电位阳离子通道M7 (transient receptor potential cation channel subfamily M member 7,TRPM7)和M6(TRPM6)对机体Mg2+稳态的调控起重要作用,其介导的Mg2+电流亦有重要生理作用[1-2].     

Effect of magnesium-deficient diet on cation transport in pregnant rabbits.

The imbalance of cation transport is considered to play an important role in the development of hypertension, and this also applies to hypertension during pregnancy. Magnesium (Mg) is one of the factors that regulate cation transport across the cell membrane. We therefore studied the effect of a magnesium-deficient diet on the activity of erythrocyte Na/K-ATPase and Mg-ATPase from six pregnant rabbits and compared the results to those obtained from six controls on a normal diet. None of the rabbits on the deficient diet developed hypertension or intrauterine growth retardation; nevertheless the activity of both enzymes was significantly reduced compared to the group on the normal diet. Since the reduced activity of these enzymes can determine sodium or calcium retention in the cell, Mg deficiency could be the basis of the onset of some forms of hypertension in pregnancy.     

The use of magnesium in bronchial asthma: a new approach to an old problem

Magnesium deficiency is a common electrolyte disorder in patients with acute severe asthma, but intracellular magnesium content better reflects its homeostasis than does its serum concentration. Magnesium takes part in many metabolic processes in the organism, including energy metabolism, protein and nucleic acid synthesis, cell cycle, the binding of substances to the plasma membrane, and maintenance of cytoskeletal and mitochondrial integrity. It also modulates ion transport and influences intracellular calcium concentration. Maintenance of the cells’ transmembrane gradient depends on the presence of magnesium, and hypomagnesemia may result in an increase in neuromuscular cell excitability. Magnesium is a cation modulating the smooth muscle contractility of different tissues: hypomagnesemia causes their contraction and hypermagnesemia their relaxation. Suggestions of a positive influence of magnesium in the treatment of asthma exacerbation have been known for a long time, but research results differ. A single dose of intravenous magnesium sulfate given to patients with acute asthma exacerbation has been shown to be safe, but its efficiency is still under discussion. According to the Global Initiative for Asthma GINA-2005, magnesium sulfate administration is not recommended for routine treatment, but it is permitted in patients with severe asthma exacerbation not responding to treatment (evidence category A). Recommendations of the British Thoracic Society allow one dose of magnesium sulfate to patients with acute severe asthma exacerbation and inadequate initial response to broncho-dilating inhalation treatment (evidence category A). Future investigations should help to establish the indications for magnesium use in the treatment of acute asthma exacerbations as well as the magnesium dose and the scheme of its administration.     

In vitro effect of magnesium on the Na/K-ATPase isolated from human placenta.

Magnesium (Mg) is an activator of many cellular processes, among which is cation transport. An imbalance of cation transport may be involved in several diseases, as well as during pregnancy. Since the action of Mg in vivo in preventing gestational diseases is known, as well as its role in vitro on some cation transport activities, we studied the action of increasing concentrations of Mg on the activity of the enzyme Na/K-ATPase isolated from placental tissue of six normotensive women, at term. Incubation in a medium with increasing concentrations of Mg resulted in a significant activation of the enzyme, which was related to Mg concentration. The study demonstrates the action of Mg in vitro on isolated enzymes, and suggests the use of enzyme purification as a model for the study of cation transport in pregnancy.     

Magnesium (Mg) status in patients with cardiovascular diseases]

Mg is the fourth most abundant total cation in the human body and the second most abundant intracellular cation. Moreover, Mg is an important cofactor for many enzymes especially those involved in phosphate transfer reactions. Mg is therefore essential in the regulation of the metabolism of other ions and cellular functions. Mg deficiency has been shown to be associated with fatal cardiovascular diseases such as cardiac arrhythmias and coronary heart disease, as well as with risk factors for these diseases, such as hypertension, and diabetes mellitus. Clinical evaluation of Mg status has been limited by the lack of suitable technology for measuring this cation. Although the measurement of serum total Mg is routinely available, ionized Mg is physiologically active. Furthermore, most of the body's Mg is present in the intracellular space. Our findings showed that serum total Mg was similar in all groups, but patients with arrhythmias and diabetes mellitus revealed lower levels of serum ionized Mg. On the other hand, patients with essential hypertension exhibited higher intraerythrocyte Mg concentrations than healthy controls. The measurement of serum total Mg may obscure the diagnosis of an abnormality in Mg metabolism in patients with arrhythmias and diabetes mellitus. Furthermore, the intracellular accumulation of Mg does not support the hypothesis of Mg deficiency in patients with essential hypertension.     

Oral magnesium supplementation improves fetal circulation.

It is well known that pregnancy is a condition in which plasma magnesium falls because of accumulation of the ion in the placenta and fetus. Magnesium (Mg) is therefore widely given as a supplement during pregnancy, particularly in cases of preterm labour. In our experience, the combination of oral Mg (magnesium pyrrolidone carboxylic acid) at a dose of 360 mg/day with conventional ritodrine treatment allows a reduction in ritodrine dosage, accompanied by a significant reduction in side effects. We therefore evaluated changes in fetal blood flow, using pulsed Doppler, in women submitted to combined magnesium and ritodrine treatment compared to those treated with ritodrine plus placebo. The Mg-treated group showed a decrease in vessel resistance both in the umbilical artery and in the fetal middle cerebral artery, indicating that fetal vasculature is sensitive to exogenous Mg. Measurement of plasma and mononuclear cell Mg showed an intracellular increase in the cation of about 10 per cent. We conclude that oral magnesium supplementation in pregnancy is safe and that it has a positive effect on the fetal circulation.     

Magnesium transport through the basal plasma membrane of larval malpighian tubules of Drosophila hydei studied by electron probe X-ray microanalysis.

Magnesium besides calcium is the most important excretion product. In the anterior Malpighian tubules of Drosophila, excretion of magnesium takes place via the hindgut by proteoglycan containing concretions. This study reports on magnesium transport through the basal plasma membrane of the principal cells of the proximal segment of the anterior Malpighian tubules. Measurements by electron probe X-ray microanalysis indicate the existence of two antiporters which transfer magnesium in still unknown stoichiometry from the hemolymph space into the cell: Mg/H and Mg/Na.     

Chloride and magnesium dependence of vasopressin release from rat permeabilized neurohypophysial nerve endings

The role of Cl- and Mg+ ions has been studied on the secretory mechanism leading to the release of vasopressin from digitonin permeabilized nerve endings isolated from the rat neurohypophysis. Secretion was triggered by challenging the permeabilized nerve endings with 1.1 microM free Ca2+. Magnesium enhances secretion and its maximal effect occurred at a concentration of about 2 mM. Further increase of this divalent cation concentration however led to an inhibition of secretion. Chloride ions are necessary for the final steps in exocytosis and this effect of Cl- was inhibited by the chloride channel antagonist N144. It is concluded that in neurosecretory nerve endings magnesium and chloride ions are crucial components for exocytosis to occur.     

Pollen development and fertilization in Arabidopsis is dependent on the MALE GAMETOGENESIS IMPAIRED ANTHERS gene encoding a type V P-type ATPase

In flowering plants, development of the haploid male gametophytes (pollen grains) takes place in a specialized structure called the anther. Successful pollen development, and thus reproduction, requires high secretory activity in both anther tissues and pollen. In this paper, we describe a novel member of the eukaryotic type V subfamily (P(5)) of P-type ATPase cation pumps, the MALE GAMETOGENESIS IMPAIRED ANTHERS (MIA) gene. MIA protein is highly abundant in the endoplasmic reticulum and small vesicles of developing pollen grains and tapetum cells. T-DNA insertional mutants of MIA suffer from imbalances in cation homeostasis and exhibit a severe reduction in fertility. Mutant microspores fail to separate from tetrads and pollen grains are fragile with an abnormal morphology and altered cell wall structure. Disruption of MIA affects expression of genes essential for secretion as well as a high number of genes encoding cell wall proteins and membrane transporters. MIA functionally complements a mutant in the P(5) ATPase homolog SPF1 from Saccharomyces cerevisiae, suggesting a common function for P(5) ATPases in single and multicellular organisms. Our results suggest that MIA is required in the secretory pathway for proper secretion of vesicle cargo to the plasma membrane.     

Unique deposits in mast cells fixed with pyroantimoanate osmium tetroxide.

Evidence for a unique cation distribution in mast cells in a variety of tissues was obtained by fixation with a modification of the potassium pyroantimonate-osmium tetroxide procedure of Komnick. Fine antimonate deposits with a heterochromatin distribution were abundant in nuclei of other cell types but were diminished to absent in mast cell nuclei. Nuclei of mast cells usually contained large coarse precipitates which measured 100–150 nm in diameter and were distributed peripherally, as well as less coarse deposits, which measured about 50 nm, and were distributed throughout the nucleus. Cytoplasmic deposits distributed in Golgi vesicles, between granules and at the plasmalemma were observed in some cells. It is suggested that these unusual deposits result from precipitation of antimonate by histamine or by cations whose distribution is affected by the highly ionic materials present in mast cells. Mast cells of man differed from those of rodents in containing cytoplasmic lipid droplets with peripheral antimonate deposits.     

Human neutrophil calprotectin reduces the susceptibility of Borrelia burgdorferi to penicillin

Borrelia burgdorferi, the spirochetal agent of Lyme disease, is susceptible to killing by a variety of polymorphonuclear leukocyte (PMN) components. Some are most effective against metabolically active B. burgdorferi. The abundant PMN cytoplasmic protein calprotectin, elevated 10- to 100-fold in inflammation, inhibits the growth of spirochetes through chelation of the essential cation, Zn. Since the action of some therapeutic antibiotics depends on bacterial division, we investigated the antibiotic sensitivities of spirochetes in calprotectin. In physiologic calprotectin, B. burgdorferi is not eliminated by therapeutic doses of penicillin G; in contrast, doxycycline is effective. Calprotectin may modify the clearance of spirochetes at sites of inflammation.     

A cation-retaining layer in the alveolar-capillary membrane.

The ultrastructural cytochemistry of the alveolar-capillary "membrane" has been investigated. Dialyzed iron and high iron diamine staining demonstrated a layer containing sulfated mucosubstance at the basal surface of the membranous pneumocytes. In the same layer, fixation with an osmium tetroxide-potassium pyroantimonate solution yielded abundant fine precipitates which were abolished by inclusion of ehtylene glycol bis-N,N'-tetraacetic acid (EGTA) in the fixative. This cation-retaining layer could be interpreted as providing a mechanism for retarding cation transport from the basement membrane to the alveolar space. High iron diamine staining also demonstrated a layer of sulfated mucosubstance on the microvilli of the granular pneumocytes. This layer corresponded with a sialidase-resistant, dialyzed iron-reactive stratum which overlaid the sialomucin-rich cell coat.     

Biogenesis of bacterial cellulose

Cellulose is the most abundant biological polymer on Earth. It is found in wood and cotton, and forms the basic structural foundation of the cell wall of almost all eukaryotic plants. Bacteria are known to secrete cellulose as part of their metabolism of glucose and other sugars. The focus of this review is upon bacterial cellulose synthesis. We emphasize recent literature directed primarily upon Acetobacter xylinum, which has been most widely studied. Our review covers the following topics relating to cellulose synthesis: genetics, biochemistry, ultrastructure, growth conditions, and ecological considerations as they relate to the diversity of microbes capable of synthesizing this abundant, unique polymer--cellulose.     

Modulation of acid-sensing ion channels by Cu(2+) in cultured hypothalamic neurons of the rat

Acid-sensing ion channels (ASICs) are known to distribute throughout the nervous system and serve important roles in various physiological and pathological processes. However, the properties of ASICs in the hypothalamus, an important region of diencephalon, are little known. We herein used whole-cell patch-clamp recordings to characterize proton-induced cation currents in cultured hypothalamic neurons of the rat, and attributed these transient inward currents to ASICs based on their electrophysiological and pharmacological properties. We further examined the effects of Cu(2+), the third most abundant trace element, on ASICs in hypothalamic neurons. Our results showed that this divalent cation reversibly and concentration-dependently inhibited the amplitude of ASIC currents, and slowed down the desensitization of ASIC channels. Our results also displayed that Cu(2+) modulated ASICs independent of change in membrane potential and extracellular protons, suggesting a noncompetitive mechanism. Furthermore, micromolar concentration of Cu(2+) attenuated the acid-induced membrane depolarization. Taken together, our data demonstrate a modulatory effect of Cu(2+) on ASICs in native hypothalamic neurons and suggest a role of this endogenous metal ion in negatively modulating the increased neuronal membrane excitability caused by activation of ASICs.     

丙戊酸镁缓释片和碳酸锂治疗少年儿童急性躁狂发作的对照研究

目的比较丙戊酸镁缓释片和碳酸锂治疗少年躁狂症的疗效及副作用。方法对72例少年儿童急性躁狂发作分别给予丙戊酸镁缓释片和碳酸锂治疗,其中丙戊酸镁缓释片36例,碳酸锂36例。疗效评定采用躁狂量表(BRMS)、临床疗效总评量表(CGI)。不良反应采用不良反应量表(TESS)。观察6周。结果丙戌酸镁缓释片组显好率、好转率分别为72.22%、88.89%,碳酸锂组显好率、好转率分别为69.44%、86.11%,两组总有效率接近。碳酸锂组恶心、震颤、EKG异常多见。结论丙戊酸镁缓释片和碳酸锂一样能有效治疗少年儿童急性躁狂发作,丙戊酸镁缓释片依从性较好。     

猪淋巴细胞E受体与SRBC结合对细胞内锌、铜、钙、镁元素含量的影响

猪的淋巴细胞E受体与SRBC结合前后,利用原子吸收光谱检测淋巴细胞内外,锌、铜、镁、钙元素水平变化,发现其上清液的锌元素含量明显高于结合前(0.27/0.18,P<0.01),而淋巴细胞内含量正相反(0.36/0.41,P<0.01),而钙元素与锌相反,E受体和配体结合后,钙元素含量较结合前减少,铜和镁元素无规律性变化,其免疫学意义有待进一步探讨。     

Magnesium as a food supplement

Magnesium is a Cofactor in all enzymes transfering phosphate. It is therefore necessary for the energymetabolism and for many synthesis, i.e. DNA and RNA. Mg is one of the most widespread elements of the earthcrust and is found in many nutritients. Nevertheless the daily intake in the western countries is often under the recommended level, due to the western life stile. Regular alcohol intake lessens the resorption and regular sport enhances the excretion via the sweat. Especially in elderly people this can lead to a lack of Magnesium. This may promote muscular cramps and weakness, cardiac arrhythmias, hypertension or bronchial hyperreactivity. It seems to be reasonable to recommend liberally a oral supplementation with magnesium.     

Magnesium deficiency alters aggressive behavior and catecholamine function

Magnesium is an abundant mineral in the brain and is important for monoamine neurotransmitter synthesis and receptor binding. It should, therefore, have behavior-altering effects. Three experiments were conducted to determine the influence of magnesium deficiencies on aggressive behavior and catecholamine function in mice. There were concentration- and time-dependent reductions in offensive aggressive behavior with magnesium deficiencies. Defensive behavior was affected in a manner opposite to that of offensive behavior. Upon administration of low doses of apomorphine and l-amphetamine, less dopamine- and norepinephrine-related behavior occurred with less magnesium in the diet. These reductions also showed a time dependency. These data demonstrate that magnesium has an influence on aggressive behavior in mice. Also, a magnesium deficiency is capable of altering the potency of catecholamine stimulating drugs.     

Die Toxizität des Aluminiums

Summary In view of the increasing pollution of our environment and forest decline, growing interest has been focused on aluminum toxicity. Aluminum is one of the most abundant metals and commonly present in tap water, beverages, food, cosmetics, and pharmaceutical preparations. Thus everybody is exposed to aluminum to a greater or lesser extent. It is now beyond any doubt that aluminum intoxication may cause encephalopathy, fracturing vitamin D resistant osteomalacia, and microcytic anemia in patients with chronic renal insufficiency as well as in experimental animals. The risk of aluminum intoxication has also to be considered in several other groups. These include elderly individuals with physiologically impaired excretory renal function who are treated with aluminum — containing antacids, patients with chronic liver disease, infants who are fed highly aluminum-contaminated formula at a time when their excretory renal function has not jet fully developed, patients on total parenteral nutrition, and, possibly, patients with Alzheimer's disease.

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Abkürzungen Al Aluminium - Cu Kupfer - Mg Magnesium - PTH Parathormon - sHPT sekundärer Hyperparathyreoidismus - PTX Parathyreoidektomie - EEG Elektroenzephalogramm - DOPA 3,4-Dihydroxyphenylalanin - TPN Total Parenteral Nutrition