Combination of Soy Protein, Amylopectin, and Chromium Stimulates Muscle Protein Synthesis by Regulation of Ubiquitin-Proteasome Proteolysis Pathway after Exercise.

The present study was undertaken to investigate the effect of the combination of soy protein, amylopectin, and chromium (SAC) on muscle protein synthesis and signal transduction pathways involved in protein synthesis (mTOR pathways, IGF-1, and AktSer473) and proteolysis (FOXO1Ser256; MURF1, MAFbx) after exercise. Thirty-five Wistar rats were randomly divided into five groups: (1) control (C); (2) exercise (E); (3) exercise + soy protein (3.1 g/kg/day) (E + S); (4) exercise + soy protein + chromium (E + S + Cr); (5) exercise + soy protein + amylopectin + chromium (E + S + A + Cr). Post-exercise ingestion of SAC significantly increased the fractional rate of protein synthesis (FSR), insulin, glycogen, and amino acid levels with the highest effect observed in E + S + A + Cr group (P Ë‚ 0.05). However, SAC supplementation decreased the lactic acid concentration (P Ë‚ 0.05). A reduction in forkhead box protein O1 (FOXO1) and forkhead box protein O3 (FOXO3) (regulators of ubiquitin-related proteolysis) and muscle atrophy F-box (MAFbx) levels was noted after treatment with SAC (P < 0.05). Insulin-like growth factor 1(IGF-1) level was increased in the E + S, E + S + Cr, and E + S + A + Cr groups (P < 0.05). While the phosphorylation of 4E-BP1Thr37/46, AktSer473, mTORSer2448, and S6K1Thr389 levels increased after SAC supplementation, phosphorylated muscle ring finger 1 (MuRF-1, an E3-ubiquitin ligase gene) was found to be significantly lower compared with the E group (P Ë‚ 0.05). These results indicate that SAC supplementation improves FSR, insulin, and glycogen levels after exercise. SAC improves protein synthesis by inhibiting the ubiquitin-proteasome pathway and inducing anabolic metabolism.

Chromium.

Two oxidation states of chromium are considered to be biologically and environmentally relevant based on their stability in the presence of water and oxygen. Compounds containing chromium(6 + ) are mutagenic and carcinogenic when inhaled and potentially when ingested orally in large quantity as well. Chromium as the trivalent will be the focus of this work as it was proposed to be an essential element for mammals ∼60 y ago; however, in the last 2 decades its status has been questioned. Chromium has been postulated to be involved in regulating carbohydrate and lipid (and potentially also protein) metabolism by enhancing insulin's efficacy (1). However, in 2014, the European Food Safety Authority found no convincing evidence that chromium is an essential element (2). Dietary chromium apparently is absorbed via passive diffusion and the extent of absorption is low (∼1%). Chromium is maintained in the bloodstream bound to the protein transferrin. It is generally believed to be delivered to tissues by transferrin via endocytosis (1). No unambiguous animal model of chromium deficiency has been established (2). One limitation in characterizing chromium deficiency in humans is the lack of an accepted biomarker of chromium nutritional status. Attempts to identify a glucose tolerance factor have not provided a chemically defined functional compound that conforms with the proposed physiologic role of chromium as a facilitator of insulin action in vivo.

[Micronutrients and diabetes, the case of minerals]. / Micronutrientes y diabetes, el caso de los minerales.

Minerals are essential nutrients for the body, are of inorganic nature which gives them the characteristic of being resistant to heat, are involved in a lot of chemical reactions in metabolism, regulating electrolyte balance, in maintaining bone, in the process of blood clotting and the transmission of nerve impulses, particularly its role as enzyme cofactors confers a key role in various physiological processes. Glucose homeostasis involves a fine coordination of events where hormonal control by insulin plays a key role. However, the role of minerals like magnesium, zinc, chromium, iron and selenium in the diabetes is less obvious and in some cases may be controversial. This review shows the knowledge of these five elements and their correlation with diabetes.

Los minerales son nutrientes esenciales para el organismo, de naturaleza inorgánica que les confiere, entre otras características, ser resistentes al calor, participan en diversas reacciones químicas del metabolismo en donde regulan el equilibrio hidroelectrolítico, el mantenimiento óseo, en la trasmisión de los impulsos nerviosos, y durante el proceso de coagulación sanguínea, particularmente por su función como cofactores enzimáticos, tienen un papel clave en varios procesos fisiológicos. La homeostasis de la glucosa involucra una fina coordinación de eventos en donde el control hormonal por la insulina tiene un papel primordial. Sin embargo, la función de los minerales, como el magnesio, el zinc, el cromo, el hierro y el selenio en la diabetes es menos evidente y puede ser, en algún caso, controversial. Esta revisión muestra el conocimiento acerca de estos cinco elementos y su correlación con la diabetes.

[Re-evaluation of the fundamentals of trace elements].

The roles of trace elements have been extensively studied for decades. However, recent advances in both molecular and epidemiological studies on trace elements have provided new information and concepts on the actions of trace elements. Some of our fundamental knowledge on the roles of trace elements based on classical data should be replaced by new concept based on new findings. This series of "Re-evaluation of the Fundamentals of Trace Elements" aims to provide new fundamentals on trace elements by reviewing rapidly advancing knowledge in this study area. The first article is a critical review on the role of chromium in human nutrition.

[Is chromium an essential trace element in human nutrition?].

It has been recognized that chromium is an essential trace element associated with carbohydrate metabolism, and chromium deficiency causes an impaired glucose tolerance. Recently, however, Vincent et al. have reported that chromium is not an essential trace element. In the present report, the author evaluated the nutritional essentiality of chromium by reviewing several previous reports. In almost all previous reports, the chromium concentration in the animal feed used was higher than 0.1 µg/g, and it is difficult to consider that the experimental animals were in a low-chromium state. In addition, the amount of chromium administered to the animals for the improvement of glucose tolerance was at a pharmacological level, and corresponded to a level that far exceeded the human daily chromium intake (20 to 80 µg/day). On the other hand, recent research has clearly shown that feeding with a severely low-chromium diet (0.016 µg/g) does not impair glucose tolerance. The amount of chromium absorbed in humans estimated from chromium intake (20 to 80 µg/day), chromium absorption rate (1%), and urinary chromium excretion (<1 µg/day) is less than 1 µg/day, which is much lower than those of other essential trace elements. In addition, because there is an inconsistency between the chromium concentration in food and chromium intake, chromium intake seems to be dependent on chromium contamination during food processing and cooking. It is concluded that there is a high possibility that chromium is not an essential trace element.

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.

Chromium and your health

Chromium is one of the most common elements that exists in the environment in several oxidation states, principally as (i) metallic (Cr0), (ii) trivalent (chromium 3+), which is biologically active and found in food and nutrition supplements (iii) hexavalent (chromium 6+), largely synthesized by the oxidation of the more common and naturally occuring trivalent chromium. This is highly toxic and used in industries. Trivalent chromium is an essential nutrient with very low toxicity, found in most food and nutrition supplements, and is required in the diet in trace or small amounts, thus it is deemed a micronutrient. Its primary function is in carbohydrate and lipid (fat) metabolism.

Chromium in metabolic and cardiovascular disease.

Chromium is an essential mineral that appears to have a beneficial role in the regulation of insulin action, metabolic syndrome, and cardiovascular disease. There is growing evidence that chromium may facilitate insulin signaling and chromium supplementation therefore may improve systemic insulin sensitivity. Tissue chromium levels of subjects with diabetes are lower than those of normal control subjects, and a correlation exists between low circulating levels of chromium and the incidence of type 2 diabetes. Controversy still exists as to the need for chromium supplementation. However, supplementation with chromium picolinate, a stable and highly bioavailable form of chromium, has been shown to reduce insulin resistance and to help reduce the risk of cardiovascular disease and type 2 diabetes. Since chromium supplementation is a safe treatment, further research is necessary to resolve the confounding data. The existing data suggest to concentrate future studies on certain forms as chromium picolinate and doses as at least 200 mcg per day.

Change in pancreatic B-cell function (HOMA-B) varies in different populations with similar genetic backgrounds but different environments.

OBJECTIVE: To determine whether pancreatic B-cell function varies in different populations with similar genetic backgrounds but different environments. RESEARCH DESIGN/METHODS: We compared a specific migrant Gujarati community in the UK (n = 205) with people still resident in the same villages of origin in Gujarat, India (n = 246). Pancreatic B-cell function (HOMA-B) was determined and the influence of age, migration and other factors was explored. RESULTS: As anticipated, there was an age-related decline in log(HOMA-B) in both groups. However, the age-related fall in log(HOMA-B) was more pronounced in the UK than in Gujarat (normalized beta-0.29 vs. -0.14, P for difference = 0.03). The decline of HOMA-B with age persisted after adjustment for body mass index (UK beta = -0.31; Gujarat beta = -0.16, P = 0.015, P < 0.001). There was no significant change in insulin sensitivity (HOMA-S) with age at either site, although insulin sensitivity was lower in the UK. Fasting non-estrified fatty acid (NEFA) levels rose with age in the UK but not in Gujarat (P = 0.003 for difference in gradients). In multiple linear regression analysis, lower log(HOMA-B) was independently associated with higher fasting log(NEFA) levels; normalized beta = -0.24, P < 0.001, age; beta = -0.16, P = 0.005, higher log(insulin-like growth factor binding protein-1); beta = -0.19, P = 0.007 and lower body mass index; beta = 0.26, P = 0.001. This model accounted for 25% of the variability in HOMA-B. CONCLUSIONS: HOMA-B as a measure of B-cell function declines more rapidly with age in the migrant UK group than in Gujarat. This may be a direct consequence of chronically higher NEFA exposure in the UK group.

DNA damage induced by a chromium(III) Schiff base complex is reversible under physiological condition.

[Cr(naphen)(H2O)(2)]+, where naphen is 1,2-bis(naphthylideneamino)ethane having the basic salen moiety, has been characterized structurally. [Cr(naphen)(H2O)(2)]+, which has an extended aromatic system and binds with calf thymus DNA (CT DNA) intercalatively, has been found to promote DNA cleavage in the presence of biological reductant such as ascorbate and oxidant like hydrogen peroxide. Results of electron paramagnetic resonance (EPR) experiments suggest involvement of hydroxyl radicals in the oxidative cleavage of DNA in the presence of the Cr(III) complex and hydrogen peroxide. The cell viability study on nicked DNA by [Cr(naphen)(H2O)(2)]+ has shown that the damage brought about to DNA could be repaired by Escherichia coli DNA repair enzymes.

Cellular chromium enhances activation of insulin receptor kinase.

Chromium has been recognized for decades as a nutritional factor that improves glucose tolerance by enhancing in vivo insulin action, but the molecular mechanism is unknown. Here we report pretreatment of CHO-IR cells with chromium enhances tyrosine phosphorylation of the insulin receptor. Different chromium(III) compounds were effective at enhancing insulin receptor phosphorylation in intact cells, but did not directly activate recombinant insulin receptor kinase. The level of insulin receptor phosphorylation in cells can be increased by inhibition of the opposing protein tyrosine phosphatase (PTP1B), a target for drug development. However, chromium did not inhibit recombinant human PTP1B using either p-nitrophenyl phosphate or the tyrosine-phosphorylated insulin receptor as the substrate. Chromium also did not alter reversible redox regulation of PTP1B. Purified plasma membranes exhibited insulin-dependent kinase activity in assays using substrate peptides mimicking sites of Tyr phosphorylation in the endogenous substrate IRS-1. Plasma membranes prepared from chromium-treated cells had higher specific activity of insulin-dependent kinase relative to controls. We conclude that cellular chromium potentiates insulin signaling by increasing insulin receptor kinase activity, separate from inhibition of PTPase. Our results suggest that nutritional and pharmacological therapies may complement one another to combat insulin resistance, a hallmark of type 2 diabetes.

A scientific review: the role of chromium in insulin resistance.

Chromium is an essential mineral that appears to have a beneficial role in the regulation of insulin action and its effects on carbohydrate, protein and lipid metabolism. Chromium is an important factor for enhancing insulin activity. Studies show that people with type 2 diabetes have lower blood levels of chromium than those without the disease. Insulin resistance is the common denominator in a cluster of cardiovascular disease risk factors. One out of every five Americans has metabolic syndrome. It affects 40% of people in their 60s and 70s. Insulin resistance, with or without the presence of metabolic syndrome, significantly increases the risk of cardiovascular disease. Insulin resistance is present in two serious health problems in women; polycystic ovarian syndrome (PCOS) and gestational diabetes. Several studies have now demonstrated that chromium supplements enhance the metabolic action of insulin and lower some of the risk factors for cardiovascular disease, particularly in overweight individuals. Chromium picolinate, specifically, has been shown to reduce insulin resistance and to help reduce the risk of cardiovascular disease and type 2 diabetes. Dietary chromium is poorly absorbed. Chromium levels decrease with age. Supplements containing 200-1,000 mcg chromium as chromium picolinate a day have been found to improve blood glucose control. Chromium picolinate is the most efficacious form of chromium supplementation. Numerous animal studies and human clinical trials have demonstrated that chromium picolinate supplements are safe.

Recent advances in the nutritional biochemistry of trivalent chromium.

The nutritional biochemistry of trivalent Cr has been a poorly understood field of study; investigations of the biochemistry of the other essential transition metals have not proven as problematic. Despite over four decades of endeavour, only recently has a picture of the role of Cr potentially started to be defined. The biologically-relevant form is the trivalent ion. Cr3+ appears to be required for proper carbohydrate and lipid metabolism in mammals, although fortunately Cr deficiency is difficult to achieve. Conditions that increase circulating glucose and insulin concentrations increase urinary Cr output. Cr is probably excreted in the form of the oligopeptide chromodulin. Chromodulin may be the key to understanding the role of Cr at a molecular level, as the molecule has been found to bind to activated insulin receptor, stimulating its kinase activity. A mechanism for the action of chromodulin has recently been proposed; this mechanism can serve as a potential framework for further studies to test the role of Cr in metabolism. An examination of the nutritional supplement chromium picolinate illustrates some of the difficulties associated with these biochemical studies.

[Chromium as an essential element]. / Chrom jako biogenní prvek.

Chromium was known for many years to be an element causing allergic reactions and having neurotoxic and carcinogenic effects. These effects can be observed especially in the case of hexavalent chromium. Only a little more than four decades ago trivalent chromium has been known as an essential element with relation to glycide and lipid metabolism. And only during several last years this chromium function has been revealed on a molecular level. After absorption in the gastrointestinal tract, chromium is most likely transported to cells bound to the plasma protein transferrin. Insulin initiates chromium transport into the cells where it is bound to the oligopeptide apochromodulin. This oligopeptide combined with four chromium(III) atoms forms chromodulin, which is important for amplifying the insulin signalling effect. After binding to insulin-activated receptor, chromodulin increases tyrosine kinase activity by one order. This enzyme forms a part of intracellular portion of insulin receptor. Chromium supplementation in people with chromium deficiency can improve glucose tolerance and some lipid metabolism parameters. The supplementation is indicated in persons with impaired glucose tolerance both in preclinical and manifested stadium of type 2 diabetes mellitus where increased lost of chromium in urine was documented. In these patients, chromium deficiency can participate in insulin resistance and hyperlipidaemia. Chromium is usually applied in the form of organic compounds: yeast extract or chromium(III) picolinate. Cr(III) picolinate can be reduced to compounds of Cr(II) in the cells which can then produce free hydroxyl radical in the so called Fenton reaction.

The potential value and toxicity of chromium picolinate as a nutritional supplement, weight loss agent and muscle development agent.

The element chromium apparently has a role in maintaining proper carbohydrate and lipid metabolism in mammals. As this role probably involves potentiation of insulin signalling, chromium dietary supplementation has been postulated to potentially have effects on body composition, including reducing fat mass and increasing lean body mass. Because the supplement is absorbed better than dietary chromium, most studies have focused on the use of chromium picolinate [Cr(pic)(3)]. Cr(pic)(3) has been amazingly popular with the general public, especially with athletes who may have exercise-induced increased urinary chromium loss; however, its effectiveness in manifesting body composition changes has been an area of intense debate in the last decade. Additionally, claims have appeared that the supplement might give rise to deleterious effects. However, over a decade of human studies with Cr(pic)(3) indicate that the supplement has not demonstrated effects on the body composition of healthy individuals, even when taken in combination with an exercise training programme. Recent cell culture and in vivo rat studies have indicated that Cr(pic)(3) probably generates oxidative damage of DNA and lipids and is mutagenic, although the significance of these results on humans taking the supplement for prolonged periods of time is unknown and should be a focus for future investigations. Given that in vitro studies suggest that other forms of chromium used as nutritional supplements, such as chromium chloride, are unlikely to be susceptible to generating this type of oxidative damage, the use of these compounds, rather than Cr(pic)(3), would appear warranted. Potential neurological effects (both beneficial and deleterious) from Cr(pic)(3) supplementation require further study.