Chromium in carbohydrate and lipid metabolism

 Since the discovery in the 1950s that mammals have a nutritional requirement for chromium, the biological function of chromium has been sought. Candidates for the naturally-occurring biologically active form of chromium have been proposed, but, until recently, all have been shown to be artifacts. Recent studies examining the properties of the oligopeptide low-molecular-weight chromium-binding substance (LMWCr) suggest that this material may have a role in carbohydrate and lipid metabolism as part of a novel insulin-signaling amplification mechanism and may have implications in the treatment of diabetes and related conditions. Received: 24 March 1997 / Accepted: 9 September 1997     

Chromium metabolism and its role in disease processes in man

Chromium is an essential element required for normal carbohydrate and lipid metabolism. Insufficient dietary Cr has been linked to maturity-onset diabetes and cardiovascular diseases. The dietary Cr intake of most individuals is considerably less than the suggested safe and adequate intake. Consumption of refined foods, including simple sugars, exacerbates the problem of insufficient dietary Cr since these foods are not only low in dietary Cr but also enhance additional Cr losses. Chromium losses are also increased due to pregnancy, strenuous exercise, infection, physical trauma and other forms of stress. Supplementation of Cr to normal free-living individuals often leads to significant improvements in glucose tolerance, serum lipids including high-density lipoprotein cholesterol, insulin and insulin binding. Chromium also tends to normalize blood sugar. Chromium supplementation of subjects with elevated blood sugar following a glucose load leads to a decrease in blood sugar while hypoglycemics respond to supplemental Cr by an increase in hypoglycemic glucose values, increased insulin binding and alleviation of hypoglycemic symptoms. In summary, dietary intake of Cr is suboptimal and this is exacerbated by increased Cr losses due to stress and certain refined foods including simple sugars that enhance Cr losses. Supplemental Cr is associated with improvements of risk factors associated with maturity-onset diabetes and cardiovascular diseases.     

Chromium(III)-insulin derivatives and their implication in glucose metabolism

Insulin has been reacted with five chromium(III) complexes that are capable of relatively facile substitution of aquo ligands. The new Cr(III) insulin derivatives have been characterized by means of electronic and infrared spectra, and evidence for major changes in the protein structure, including the state of aggregation, has been presented. Supporting evidence for the arguments favoring the beneficiary role of chromium(III) in glucose metabolism has been obtained using in vivo studies, and it has been shown that insulin derived with Cr(salen) (H2O)2+ is capable of reversing the blood sugar, serum cholesterol, and phospholipids levels to those of normal rats. The results emphasize the dependence of biopotency on the structure of Cr(III) complexes used for derivation of insulin and discount the postulates that Cr(III) serves to assemble insulin and receptor units through metal-sulphur bonding. The influence of Cr(III) on the structural stability and state of aggregation of insulin and their possible role in glucose metabolism is discussed.     

Chromium in plants

Chromium is an essential trace element and is associated with some biological pathways, especially with glucose tolerance. For these reasons, we decided to determine the concentration of chromium in two sets of Brazilian medicinal plants. The first group consisted of plants that are considered as antidiabetic, whereas the second included plants that do not have this therapeutic property. The concentration of chromium was determined by flameless atomic absorption. All the plants analyzed contain chromium in the normal range for this element, but the hypoglycemic plants contain more chromium than the others (1–4 μg/g compared to 0.5–1.5 μg/g).     

Chromium in the elderly

Several studies indicate that glucose tolerance improves and lipid levels decline in the elderly after supplementation with Cr-rich brewer's yeast or inorganic Cr. Other studies report equivocal results or no changes. Interpretation of these investigations is hampered by

1. Lack of a marker to identify Cr-deficient people
2. Artifactually high levels of dietary and body Cr, owing to inadequate analytic techniques and
3. The interplay of chronic health problems, medications, institutionalization, and dietary practices.

Investigators have studied the effects of aging on Cr in the body. In the rat, tissue retention of⁵¹Cr decreases, and organ distribution changes with age. In humans, plasma Cr levels of healthy eldery subjects are not different from those of young adults. There is no evidence of malabsorption in aged humans or animals. Nevertheless, higher urinary Cr losses are reported in elderly people. These data suggest that Cr retention may decrease with aging and that aging may alter Cr metabolism. Diets of many healthy elderly people contain <30 μg Cr. Two elderly men living under controlled conditions maintained Cr balance with 37 μg/d. However, these levels may be insufficient during the stresses and illnesses associated with aging.     

Chromium and genomic stability

Many metals serve as micronutrients which protect against genomic instability. Chromium is most abundant in its trivalent and hexavalent forms. Trivalent chromium has historically been considered an essential element, though recent data indicate that while it can have pharmacological effects and value, it is not essential. There is no data indicating that trivalent chromium promotes genomic stability and, instead may promote genomic instability. Hexavalent chromium is widely accepted as highly toxic and carcinogenic with no nutritional value. Recent data indicate that it causes genomic instability and also has no role in promoting genomic stability.     

铬与胰岛素敏感性

铬可以提高动物机体组织对胰岛素的敏感性,但对其具体作用机制直到最近才有了较深入的认识.铬在吸收后主要由转铁蛋白运输.血液胰岛素水平升高可以促进转铁蛋白受体从细胞内的小泡中移位到细胞膜上.携带铬的转铁蛋白与细胞膜表面的转铁蛋白受体发生结合,通过内吞作用将铬转运到细胞内.在细胞内,内吞小泡中的酸性环境可使铬从转铁蛋白中释放,4个三价铬离子与apochromodulin形成有活性的holochromodulin. Holochromodulin 除了可与胰岛素和/或胰岛素受体直接结合起作用外,还可以通过激活AMPK激酶来降低细胞膜胆固醇含量,改善细胞骨架功能,促进GLUT4移位,然后又通过激活p38MAPK激酶增强GLUT4的内在活性,从而促进葡萄糖吸收.但其具体分子机制仍不完全清楚.本文就铬在提高动物机体组织对胰岛素的敏感性的作用机制问题进行综述.     

Chromium in Postmortem Material

Recently, considerable attention has been paid to the negative effects caused by the presence and constant increase in concentration of heavy metals in the environment, as well as to the determination of their content in human biological samples. In this paper, the concentration of chromium in samples of blood and internal organs collected at autopsy from 21 female and 39 male non-occupationally exposed subjects is presented. Elemental analysis was carried out by an electrothermal atomic absorption spectrometer after microwave-assisted acid digestion. Reference ranges of chromium in the blood, brain, stomach, liver, kidneys, lungs, and heart (wet weight) in the population of Southern Poland were found to be 0.11–16.4 ng/mL, 4.7–136 ng/g, 6.1–76.4 ng/g, 11–506 ng/g, 2.9–298 ng/g, 13–798 ng/g, and 3.6–320 ng/g, respectively.     

Chromium Reducing and Plant Growth Promoting Potential of Mesorhizobium Species under Chromium Stress

Chromium-reducing and plant growth–promoting potential, including production of siderophores by chromium(VI)-resistant Mesorhizobium species RC1 and RC4, isolated from chickpea nodules, was assessed both in the presence and absence of chromium(VI) under in vitro conditions. The Mesorhizobium strains displayed a high level of tolerance to chromium (400 μg ml^{? 1}), and showed a varied sensitivity to antibacterial drugs, on yeast extract mannitol (YEM) agar plates. Mesorhizobium strains RC1 and RC4 reduced chromium(VI) by 84% and 83%, respectively at pH 7 in YEM broth after 120 h of incubation. Mesorhizobial strains RC1 and RC4 produced 27 and 35 μg ml^{? 1} of indole acetic acid (IAA), respectively, in Luria-Bertani broth with 100 μg ml^{? 1} of tryptophan. The IAA production by the mesorhizobial strains did not differ significantly (p ≤ .05) under chromium stress and showed a positive reaction for siderophore, HCN, and ammonia, both in the absence and presence of chromium(VI).The present observations suggest that the chromium reducing and plant growth promoting activities of the Mesorhizobium strains could be exploited for bioremediation of chromium(VI) and to enhance the legume productivity for chromium-contaminated soils.     

氯化铬和吡啶羧酸铬在Caco-2细胞中的摄取和转运

采用一种体外培养的人小肠上皮细胞模型Caco-2研究了时间、浓度、温度对氯化铬和吡啶羧酸铬细胞摄取和跨细胞转运的影响。旨在探讨氯化铬和吡啶羧酸铬在小肠上皮细胞中的摄取和转运特点。结果表明:Caco-2细胞对氯化铬和吡啶羧酸铬的摄取和转运随浓度、时间而成线性增加,当温育温度从37℃降到4℃时,摄取和转运有下降趋势(P>0.05)。氯化铬和吡啶羧酸铬从肠腔侧(AP侧)到基底侧(BL侧)的表观通透系数(Papp)近似于BL侧到AP侧(分别为0.95～1.41倍和0.84～1.07倍)。氯化铬和吡啶羧酸铬的摄取率分别为(0.88±0.08)%和(4.73±0.60)%,转运率分别为(2.11±0.05)%和(9.08±0.25)%。结果提示氯化铬和吡啶羧酸铬是以被动扩散为主要方式被Caco-2细胞摄取和转运。     

Chromium reduction in Pseudomonas putida

Reduction of hexavalent chromium (chromate) to less-toxic trivalent chromium was studied by using cell suspensions and cell-free supernatant fluids from Pseudomonas putida PRS2000. Chromate reductase activity was associated with soluble protein and not with the membrane fraction. The crude enzyme activity was heat labile and showed a Km of 40 microM CrO4(2-). Neither sulfate nor nitrate affected chromate reduction either in vitro or with intact cells.     

Plant Screening for Chromium Phytoremediation

Thirty-six plant species of different agronomic importance, size, dry matter production, and tolerance to heavy metals were evaluated for Cr(III) and Cr(VI) uptake and accumulation as influenced by rate, form, source, and chelate application to a Cr-contaminated soil. There was a significant difference in the degree of tolerance, uptake, and accumulation of Cr among plant species. Sunflower (Helianthus annuus) was the least tolerant to Cr, and Bermudagrass (Cynodon dactylon) and switchgrass (Panicum virgatum) were the most tolerant. Indian mustard (Brassica juncea, cv 426308) and sunflower accumulated more Cr than other agricultural plant species. There was no inhibition of growth and little Cr accumulation in the presence of Cr(III) in soil, but most of the plant species that were treated with Cr(VI) hyperaccumulated Cr and died. EDTA chelate added to soil enhanced Cr(III) accumulation in some plants. The phytoremediation potential of the plant species tested was limited because Cr was accumulated in the plant roots and a high concentration in the shoots was toxic to plants. The difference in behavior between Cr(III) and Cr(VI) and their importance in soil and environment contamination should be the basis for remediation strategies.

     

Efficacy of Dietary Chromium (III) Supplementation on Tissue Chromium Deposition in Finishing Pigs

The study was conducted to evaluate the efficacy of different forms of trivalent chromium (Cr) supplementation on tissue chromium deposition in finishing pigs. A total of 96 pigs with an initial average body mass 65.57±1.05 kg were blocked by body mass and randomly assigned to four treatments with three replicates. Pigs were offered one of four diets including a control diet or the control diet supplemented with 200 μg/kg chromium from either chromium chloride (CrCl(3)), chromium picolinate (CrPic) or chromium nanocomposite (CrNano) for 40 days. During the trial, all pigs were given free access to feed and water. After feeding trial, eight pigs from each treatment were slaughtered for samples collection. The results showed that supplemental CrNano increased Cr content in blood, longissimus muscle, heart, liver, kidney, jejunum, and ileum (P<0.05). Supplemental Cr from three sources increased Cr excretion from all feces (P<0.05). Urinary Cr excretion was increased by CrNano or CrPic supplementation significantly. These results suggested that chromium nanocomposite exhibited more effective on tissue Cr deposition in pigs, which indicated higher absorption compared with CrCl(3) and CrPic.     

Potential of Live Spirulina platensis on Biosorption of Hexavalent Chromium and Its Conversion to Trivalent Chromium

Microalga biomass has been described worldwide according their capacity to realize biosorption of toxic metals. Chromium is one of the most toxic metals that could contaminate superficial and underground water. Considering the importance of Spirulina biomass in production of supplements for humans and for animal feed we assessed the biosorption of hexavalent chromium by living Spirulina platensis and its capacity to convert hexavalent chromium to trivalent chromium, less toxic, through its metabolism during growth. The active biomass was grown in Zarrouk medium diluted to 50% with distilled water, keeping the experiments under controlled conditions of aeration, temperature of 30°C and lighting of 1,800 lux. Hexavalent chromium was added using a potassium dichromate solution in fed-batch mode with the aim of evaluate the effect of several additions contaminant in the kinetic parameters of the culture. Cell growth was affected by the presence of chromium added at the beginning of cultures, and the best growth rates were obtained at lower metal concentrations in the medium. The biomass removed until 65.2% of hexavalent chromium added to the media, being 90.4% converted into trivalent chromium in the media and 9.6% retained in the biomass as trivalent chromium (0.931 mg.g^?1).     

Urinary Chromium Excretion in Response to an Insulin Challenge Is Not a Biomarker for Chromium Status

Over 50 years ago, chromium (Cr) was proposed to be an essential trace element; however, recent studies indicate that this status should be removed as the effects of Cr supplementation appear to be pharmacological rather than nutritional. The pharmacological basis for Cr's effects can explain the inability of investigators to discover a biomarker for Cr status. One potential biomarker has not been examined to date. Cr is known to be mobilized in the body in response to insulin (or insulin release in response to a glucose challenge), resulting in an increase in urinary Cr excretion. The magnitude of increase in urinary Cr loss as a function of dietary Cr intake was tested as a potential biomarker for Cr. Zucker lean rats housed in carefully controlled metal-free conditions were provided a series of purified diets containing variable Cr contents (from 16 μg/kg diet to 2,000 μg/kg) for 23 weeks. The 16 μg/kg diet contained less Cr than any diet examined to date. Urine samples were collected before and after insulin and glucose challenges (0, 2, 6, and 12 h postinjection). Urinary Cr levels were analyzed by the standard method of addition using graphite furnace atomic absorption. The rate of urinary Cr loss after a glucose or insulin challenge was found to not be dependent on the Cr content of the rats' diets. Blood iron levels of the rats were also measured to determine if the addition of Cr to the diet altered iron status. The Cr content of the diet was found to have no affect on blood iron levels. Overall, the study demonstrated that insulin-stimulated urinary Cr excretion cannot be used as a biomarker for Cr status.     

Chromium and human low-density lipoprotein oxidation

Chromium is a catalytic metal able to foster oxidant damage, albeit its capacity to induce human LDL oxidation is to date unkown. Thus, we have investigated whether trivalent and hexavalent chromium, namely Cr(III) and Cr(VI), can induce human LDL oxidation. Cr(III) as CrCl₃ is incapable of inducing LDL oxidation at pH 7.4 or 4.5. However, Cr(III), specifically at physiological pH of 7.4 and in the presence of phosphates, causes an absorbance increase at 234 resembling a spectrophotometric kinetics of LDL oxidation with a lag- and propagation-like phase. In this regard, it is conceivable that peculiar Cr(III) forms such as Cr(III) hydroxide and, especially, Cr(III) polynuclear hydroxocomplexes formed at pH 7.4 interact with phosphates generating species with an intrinsic absorbance at 234 nm, which increases over time resembling a spectrophotometric kinetics of LDL oxidation. Cr(VI), as K₂Cr₂O₇, can instead induce substantial human LDL oxidation at acidic pH such as 4.5, which is typical of the intracellular lysosomal compartment. LDL oxidation is related to binding of Cr(VI) to LDL particles with quenching of the LDL tryptophan fluorescence, and it is inhibited by the metal chelators EDTA and deferoxamine, as well as by the chain-breaking antioxidants butylated hydroxytoluene and probucol. Moreover, Cr(VI)-induced LDL oxidation is inhibited by mannitol conceivably by binding Cr(V) formed from LDL-dependent Cr(VI) reduction and not by scavenging hydroxyl radicals (OH); indeed, the OH scavengers sodium formate and ethanol are ineffective against Cr(VI)-induced LDL oxidation. Notably, heightened LDL lipid hydroperoxide levels and decreased LDL tryptophan fluorescence occur in Cr plating workers, indicating Cr-induced human LDL oxidation in vivo. The biochemical, pathophysiological and clinical implications of these novel findings on chromium and human LDL oxidation are discussed.     

Chromium enhances insulin responsiveness via AMPK

Trivalent chromium (Cr³⁺) is known to improve glucose homeostasis. Cr³⁺ has been shown to improve plasma membrane-based aspects of glucose transporter GLUT4 regulation and increase activity of the cellular energy sensor 5’ AMP-activated protein kinase (AMPK). However, the mechanism(s) by which Cr³⁺ improves insulin responsiveness and whether AMPK mediates this action is not known. In this study we tested if Cr³⁺ protected against physiological hyperinsulinemia-induced plasma membrane cholesterol accumulation, cortical filamentous actin (F-actin) loss and insulin resistance in L6 skeletal muscle myotubes. In addition, we performed mechanistic studies to test our hypothesis that AMPK mediates the effects of Cr³⁺ on GLUT4 and glucose transport regulation. Hyperinsulinemia-induced insulin-resistant L6 myotubes displayed excess membrane cholesterol and diminished cortical F-actin essential for effective glucose transport regulation. These membrane and cytoskeletal abnormalities were associated with defects in insulin-stimulated GLUT4 translocation and glucose transport. Supplementing the culture medium with pharmacologically relevant doses of Cr³⁺ in the picolinate form (CrPic) protected against membrane cholesterol accumulation, F-actin loss, GLUT4 dysregulation and glucose transport dysfunction. Insulin signaling was neither impaired by hyperinsulinemic conditions nor enhanced by CrPic, whereas CrPic increased AMPK signaling. Mechanistically, siRNA-mediated depletion of AMPK abolished the protective effects of CrPic against GLUT4 and glucose transport dysregulation. Together these findings suggest that the micronutrient Cr³⁺, via increasing AMPK activity, positively impacts skeletal muscle cell insulin sensitivity and glucose transport regulation.     

Chromium incorporated in RNA and DNA

The objective of this study was to examine the effect of Cr(III) (chromium chloride) and Cr(VI) (potassium dichromate) on RNA and DNA-chromium adducts formation in isolated nucleic acids and isolated pig lymphocytes. The incubation of cells with potassium dichromate and chromium chloride at concentrations of 10 and 100 microM results in binding of a 1.2-1.9 fold greater number of chromium atoms to nuclear DNA than to total cellular RNA. The incubation of total cellular RNA and nuclear DNA isolated from lymphocytes with CrCl3 and K2Cr2O7 yielded a binding of 1.1-1.6 fold more of Cr atoms to RNA than to DNA. The number of chromium atoms bound to nucleic acids is higher after incubation with K2Cr2O7 than with CrCl3 in both experimental systems.     

Chromium content of foods and diets

Comparatively few valid data are available on the chromium content of foods and on the dietary chromium (Cr) intake of various populations. This is chiefly because of the difficulties encountered in contamination control during sampling, sample pretreatment, and analysis. Moreover, there are several analytical problems involved that are mostly owing to the low concentration level of Cr in foods. However, with the recent establishment of food reference materials with certified low concentrations of Cr, the analytical validity of studies on Cr content of foods and on its dietary intake by various populations can be ascertained. With the exception of herbs and condiments, and certain other special food items with a relatively low average consumption rate, such as tea, coffee, and some candies, most foods contain Cr below 100 μg/kg. Staple foods, particularly cereals and milk, are very low (≤10 μg/kg) in Cr, showing little or no geographic variation. Food processing may increase food Cr content depending on the process. Processes, such as meat grinding and homogenization using stainless-steel equipment, very strongly increase the Cr content of foods. Also, acidic fruit juices in contact with steel cans are high in Cr, whereas cooking in aluminium vessels reduces the Cr content of foods. Average dietary Cr intake seems to fluctuate considerably among countries. In many developing countries, such as Brazil, the Sudan, and Iran, the dietary intake is high, from 50–100μg/d, whereas in certain developed countries, such as Finland, Sweden, Switzerland, and the US, the intake is 50 μg/d or lower and, consequently, at or below the estimated safe and adequate daily dietary intake range of 50–200 μg/d established by the US National Academy of Sciences. The average Cr content of human milk is below 0.5 μg/L, thus resulting in a very low average intake of 0.3 μg Cr/d by exclusively breast-fed infants in the US and Finland.