Dietary Copper Research Articles

Dietary Determinants Of The White Blood Cell Count

IntroductionWhite blood cells are key components of the immune system. They defend the body against a host of diseases and infections. Various studies have explored the possible influence of dietary nutrients on the white blood cell (WBC) count. If it can be demonstrated that nutrients affect the WBC count, they may offer an inexpensive way of modulating the immune system and in turn, the body's ability to fight against disease and infection. The sample sizes of previous studies, however, have been relatively small. The results have therefore been variable and conflicting. The purpose of this study is to continue to explore the dietary determinants of the WBC count, using a database that allows for a larger sample size, the 2005-2006 National Health and Nutrition Health Survey (NHANES). MethodsThe main outcome variable, WBC count, was recoded to the normal range for ages ≥ 18 years, of 4-11(±2). This was done in order to account for extreme values; particularly high and low values secondary to disease or infection. The population means and 95% confidence intervals were obtained using the statistical weights for the key variables of interest (Table 1). Multiple linear regression and backward elimination were used to predict the final model (Table 2). Variables with p < 0.1 were kept in the model. SAS 9.3 was used for all statistical analyses. ResultsAssociations for age, gender, race and Body Mass Index (BMI) and WBC count, were consistent with previous studies and were all statistically significant (p< 0.0001). It has been shown that more intense physical activity usually leads to an increase in the WBC count. In this study, however, more vigorous forms of activity were associated with a lower WBC count (p < 0.0001). Increases in dietary copper and iron were associated with a subsequent decrease in the WBC count (Table 2, p < 0.05). An increase in vitamin K was also associated with a decrease in WBC count, however, it was not statistically significant (Table 2, p > 0.05). Increases in vitamin B1 were associated with an increase in WBC count (p < 0.05). ConclusionThe results of this study suggest that further prospective studies are needed to investigate the role of these nutrients as determinants of the WBC count. Disclosures:No relevant conflicts of interest to declare.

Effects of dietary copper sources on growth, tissue copper accumulation and physiological responses of Japanese sea bass (Lateolabrax japonicus) (Cuvier, 1828) fed semipurified or practical diets

An 8-week trial was conducted to compare the efficacy of a chelated copper (Cu) with the inorganic Cu (CuSO4), in the diet of Japanese sea bass (Lateolabrax japonicus). Six diets were prepared based on two basal diets (semi-purified or practical) at two Cu inclusion levels (0 and 4 mg kg−1 from or chelated-Cu), accordingly named as S0, SI4, SM4, P0, PI4 and PM4 respectively. Each diet was fed to quadruplicate groups of Japanese sea bass (initial weight: 65.0 ± 0.03 g) during the trial. Fish fed practical diets had higher feed intake, specific growth rate, protein efficiency rate (PER), liver Cu accumulation, liver Na+K+-ATPase and plasma alkaline phosphatase, but lower hepatosomatic index than the groups fed semi-purified diets (P < 0.05). Higher PER was exhibited by fish fed chelated-Cu diets than that of fish fed CuSO4 diets (P < 0.05). Although liver Cu accumulation was significantly higher in fish fed practical diets,, liver Cu content increased significantly with increasing dietary copper levels only in fish fed semipurified diets. Chelated-Cu has higher efficiency than CuSO4 when fed in practical diets. Poor growth performance of fish fed semipurified diets might induce underestimating the nutrient requirement of Japanese sea bass.

Relationship between Dietary Magnesium, Manganese, and Copper and Metabolic Syndrome Risk in Korean Adults: The Korea National Health and Nutrition Examination Survey (2007–2008)

Recent studies have reported correlations between mineral intake and metabolic syndrome (MS), but accurate relationships and consistency in the results are difficult to confirm. Accordingly, this study aims to assess the dietary intakes of magnesium (Mg), manganese (Mn), and copper (Cu) to determine their relationship with MS. Data from a total of 5,136 adults (2,084 men, 3,052 women) was collected from the 2007-2008 Korea National Health and Nutrition Examination Survey (KNHANES), and the intakes of Mg, Mn, and Cu of the MS patients were compared with those of healthy adults. The relationship between the intakes of these minerals and the MS risks was analyzed. Diagnosis of MS was evaluated by the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) standards. Among all study subjects, 25.9 % (540 subjects) of the men and 24.5 % (748 subjects) of the women met diagnostic criteria for inclusion in the MS group. In the men, daily intakes of Mg and Cu in the MS group were significantly lower than those in control group, and in the women, daily intakes of energy, Mg, Mn, and Cu in the MS group were significantly lower than those of the control group. The women subjects with high blood pressure showed significantly lower intakes of Mg, Mn, and Cu than control subjects. In addition, in the women, the highest quartile of Mg and Cu was inversely associated with MS, but with adjustment were not maintained. However, in the postmenopausal women, MS was significant and inversely associated with the highest quartiles of Cu intake and the association remained significant after adjustments. Considering that MS incidence increases and dietary intake and nutrient density decrease with increasing age, and mineral intake is reduced accordingly, these results suggest that meal management with adequate mineral intake is advisable to control MS.

Two cases of Wilson–Konovalov disease

Wilson–Konovalov disease (hepatolenticular degeneration) is a monogenic autosomal recessive genetic disorder. For its pathogenesis, there is the underlying genetic disorder of copper metabolism in which copper accumulates in excessive amounts in target organs, primarily in the liver and cerebral basal ganglia. The disease more commonly manifests at a young age and, when untreated, progresses rapidly to death. At the same time, hepatolenticular degeneration is one of a few of hereditary diseases for which an effective pathogenetic therapy with copper-eliminating medications has been developed to reduce the amount of dietary copper and to remove its excess from the body. The paper describes two patients with the rigid-arrhythmic-hyperkinetic and trembling-rigid forms of Wilson–Konovalov disease.

Accumulation and detoxification of copper and zinc by the decapod crustacean Palaemonetes varians from diets of field-contaminated polychaetes Nereis diversicolor

In an investigation of the trophic transfer of ecotoxicologically significant amounts of trace metals from prey to predator, Palaemonetes varians were fed with diets of Nereis diversicolor from two metal-contaminated estuaries, the Tavy and Restronguet Creek in SW England, and a control estuary, the Blackwater in SE England. The decapods accumulated increased concentrations of copper (but not zinc) from the metal-contaminated worms above an initial apparently regulated body copper concentration, in response to a high dietary copper input over a period up to 30days. High dietary challenges of copper caused the induction of MTLP (metallothionein-like proteins) in the hepatopancreas of the feeding decapods as a detoxification response, although the non-detoxified subcellular component of hepatopancreas accumulated copper also increased over time, probably in association with sublethal toxic effects.

A meta-analysis of the effects of dietary copper, molybdenum, and sulfur on plasma and liver copper, weight gain, and feed conversion in growing-finishing cattle1

The minerals Cu, Mo, and S are essential for metabolic functions related to cattle health and performance. The interaction between Cu, Mo, and S can determine the utilization of each mineral, in particular Cu, by ruminants. A meta-analysis was performed to evaluate the effects of dietary Cu, Mo, and S and their interactions on plasma and liver Cu, ADG, and G:F in growing-finishing cattle. Data were collated from 12 published studies. The model with the best fit to data indicated plasma Cu was positively affected by dietary Cu (P < 0.01) and negatively affected by both dietary Mo (P < 0.01) and S (P < 0.01). Another model also indicated that plasma Cu concentration is positively related to Cu:Mo ratio in the diet (P < 0.01). Dietary Cu had a positive effect on liver Cu (P < 0.01), whereas Mo showed a negative effect (P < 0.05), and no effect of dietary S on liver Cu was observed (P > 0.05). Average daily gain was negatively affected by dietary Mo (P < 0.05) and S (P < 0.01) and positively affected by Cu:Mo ratio (P < 0.01), likely because an increased Cu:Mo ratio minimizes the antagonistic effect of Mo on Cu. The feed conversion ratio was negatively affected by Mo (P < 0.05) and S (P < 0.01), whereas effects of the Cu:Mo ratio and dietary Cu were not significant (P > 0.05). The interaction between S and Mo affected (P < 0.01) G:F, which was likely related to a positive response with the proper balance between these minerals. In conclusion, dietary Cu, Mo, and S and the Cu:Mo ratio caused changes in plasma Cu. Only dietary Mo and S led to a negative response in the performance of growing-finishing cattle, whereas the diet Cu:Mo ratio has a linear and quadratic effect on ADG. Nutritionists and producers need to consider with caution the supplementation of growing-finishing cattle diets with Mo and S because of their potentially adverse effects on animal performance. An appropriate Cu:Mo ratio is desirable to minimize the effects of an impaired supply of Mo on Cu metabolism and ADG.

A metaanalysis of the effects of dietary copper, molybdenum, and sulfur on plasma and liver copper, weight gain, and feed conversion in growing-finishing cattle

A metaanalysis of the effects of dietary copper, molybdenum, and sulfur on plasma and liver copper, weight gain, and feed conversion in growing-finishing cattle

Effects of Dietary Copper on Growth, Digestive, and Brush Border Enzyme Activities and Antioxidant Defense of Hepatopancreas and Intestine for Young Grass Carp (Ctenopharyngodon idella)

To investigate the effects of dietary copper (Cu) on fish growth, digestive and absorptive enzyme activities, and antioxidant status in the hepatopancreas and intestine, young grass carp (Ctenopharyngodon idella) (282±2.8 g) were fed six diets containing 0.74 (basal diet), 2.26, 3.75, 5.25, 6.70, and 8.33 mg Cu /kg diet for 8 weeks. Results showed that percentage weight gain (PWG) and feed intake were increased with dietary Cu levels up to 3.75 mg/kg diet. In addition, the positive effects of dietary Cu at a level 3.75 or 5.25 mg/kg diet on trypsin, chymotrypsin, and lipase activities in the hepatopancreas and of Na(+), K(+)-ATPase, alkaline phosphatase, creatine kinase, and γ-glutamyl transpeptidase activities in three intestine segments produced significantly (P<0.05) better feed efficiency (FE). However, amylase activity in the hepatopancreas was decreased by dietary Cu levels up to 3.75 mg/kg diet (P<0.05). In addition, dietary Cu at 3.75 or 5.25 mg/kg diet decreased malondialdehyde and protein carbonyl content partly by significantly (P<0.05) increasing the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and glutathione content in the hepatopancreas and intestine. Collectively, dietary Cu improved growth and digestive and absorptive capacity and decreased lipid peroxidation and protein oxidation partly by enhancing antioxidant defense in the hepatopancreas and intestine. The dietary Cu requirement for PWG, plasma ceruloplasmin activity, and FE of young grass carp (282-688 g) were 4.78, 4.95, and 4.70 mg/kg diet, respectively.

Huntington disease arises from a combinatory toxicity of polyglutamine and copper binding

Huntington disease (HD) is a progressive neurodegenerative disorder caused by dominant polyglutamine (polyQ) expansion within the N terminus of huntingtin (Htt) protein. Abnormal metal accumulation in the striatum of HD patients has been reported for many years, but a causative relationship has not yet been established. Furthermore, if metal is indeed involved in HD, the underlying mechanism needs to be explored. Here using a Drosophila model of HD, wherein Htt exon1 with expanded polyQ (Htt exon1-polyQ) is introduced, we show that altered expression of genes involved in copper metabolism significantly modulates the HD progression. Intervention of dietary copper levels also modifies HD phenotypes in the fly. Copper reduction to a large extent decreases the level of oligomerized and aggregated Htt. Strikingly, substitution of two potential copper-binding residues of Htt, Met8 and His82, completely dissociates the copper-intensifying toxicity of Htt exon1-polyQ. Our results therefore indicate HD entails two levels of toxicity: the copper-facilitated protein aggregation as conferred by a direct copper binding in the exon1 and the copper-independent polyQ toxicity. The existence of these two parallel pathways converging into Htt toxicity also suggests that an ideal HD therapy would be a multipronged approach that takes both these actions into consideration.

Copper content of staple seeds and grains grown in Kanam local government area, Nigeria.

Copper is a trace mineral that plays an important role in human metabolism, largely because it allows many critical enzymes to function properly. Little is known of copper content of Nigerian foods. In this paper, copper contents of several typical Nigerian foods were determined. The samples were collected from Kanam of Plateau State in central region of Nigeria. The samples were wet-ashed according to the protocol of Hill et al. (Anal Chem 55:2340–2342, 1986).Concentrations of copper in the samples was determined using inductively coupled-mass spectrophotometry. There is, for each crop, a wide variation in copper content. The highest copper content was found in cowpea, Vigna unguiculata (16.95 μg/g of dry weight). Lowest copper content was found in white maize and in yellow maize (Zea mays), with values 1.23 μg/g and 1.38 μg/g of dry weights, respectively. Other foods, such as white sorghum, red sorghum (Sorghum bicolor), millet (Pennisetum glaucum), and groundnuts (Arachis hypogea) had copper contents varying from 2.22 to 11.81 μg/g. These values are well below the supplemental values of 50 mg/day that could interfere with zinc absorption. Thus, among the staple foodstuffs of the areas sampled, cowpea appears to be the richest source of dietary copper followed by groundnut while the two maize varieties are the poorest.

The Insufficiency Intake of Dietary Micronutrients Associated with Malnutrition-Inflammation Score in Hemodialysis Population

The relations between dietary micronutrient, nutritional status and inflammation in hemodialysis patients are still unclear. A cross-sectional study was performed in hemodialysis population. 75 hemodialysis patients from South China participated in the dietary and nutritional assessment. Clinical and dietary data were collected. Nutritional status was assessed by Malnutrition-Inflammation Score (MIS) in addition to related anthropometric measurements. And according to the MIS score, the whole hemodialysis patients were divided into normal nutrition group and malnutrition group. The results showed that mid arm circumference (MAC) negatively correlated with MIS (r = −0.425; P = 0.002). The area under the ROC curve (AUC) for MAC was 0.737 (0.614–0.859). Comparing with the normal nutritional group, lower dietary selenium (Se), copper (Cu), iodine (I) and manganese (Mn) intake were observed among patients with malnutrition (P<0.05). While no significant differences of diverse vitamins were found. In conclusion, MAC was effective indicator for assessing nutritional and inflammatory status (P<0.05). The reduction of dietary Se, Cu, I and Mn intake level may be alarming markers for malnutrition and inflammatory status in hemodialysis patients.

Hornhaut-Schlüsselbefunde im Kindesalter als Hinweis für therapierbare systemische Stoffwechselerkrankungen

Many systemic lysosomal storage disorders show basic corneal opacities already in childhood. The lysosome is a cell organelle, produced by Golgi's apparatus, that is surrounded by a membrane and contains hydrolytic enzymes that break down food molecules, especially proteins and other complex molecules. The ophthalmologist's precise diagnosis of corneal clouding at the slit-lamp may reveal the correct interpretation of the specific lysosomal storage disorder. It is very important to diagnose such diseases as soon as possible because today the development of systemic enzymatic therapies has broadened the therapeutic armamentarium for the current standard of care. The following corneal landmarks of systemic storage diseases and of the modern systemic therapy are presented: cornea verticillata in Fabry's disease, periodic infusion of alpha-galactosidase a; Kayser-Fleischer's ring in Wilson's disease, zinc, trienetin, low copper diet; multiple, punctiform crystals in cystinosis, cysteamine, Raptor RP 103(DR cysteamine) that reduces the cytotoxity in form of continous dissolving of cystine from lysosome, renal transplantation, haematopoietic stem cell transplantation; peripheral ring, but not true lipid arc, and moderate stromal haze in LCAT-deficiency, injection of recombinant enzyme or of encapsulated LCAT-secreting cells; diffuse stromal haze in mucopolysaccharidoses (MPS). Enzyme replacement therapy is currently indicated for MPS I, MPS II, and MPS VI, haematopoietic stem cell transplantation; painful, bilateral pseudo-dendritic opacities in tyrosinemia type II (eponym: Richner-Hanhart syndrome), low phenylalanine and tyrosine diet result in complete disappearance of corneal alterations with a consecutive painfree period. Strict diet during the whole life is necessary to prevent corneal recurrences and the occurrence of palmo-plantar keratoses. Such therapies can enable the patient to lead an otherwise normal life for decades.

Modest fructose beverage intake causes liver injury and fat accumulation in marginal copper deficient rats

ObjectiveDietary fructose and copper interaction may play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In this study, we investigate whether or not modest fructose consumption (3% fructose, w/v) (which is more closely related to the American lifestyle with regard to sugar beverage consumption) affects copper status, and causes liver injury and fat accumulation in marginal copper deficient rats.Design and MethodsMale weanling Sprague-Dawley rats were fed either an adequate copper (6ppm) or a marginally copper deficient (1.6ppm) diet for 4 weeks. Deionized water or deionized water containing 3% fructose (w/v) was given ad lib.ResultsModest fructose consumption further impaired copper status in the marginal copper deficient rats and increased hepatic iron accumulation. Liver injury and fat accumulation were significantly induced in the marginal copper deficient rats exposed to fructose.ConclusionsOur data suggest that modest fructose consumption can impair copper status and lead to hepatic iron overload, which in turn, may lead to liver injury and fatty liver in marginal copper deficient rats. This study provides important information on dietary fructose and copper interaction, suggesting that dietary fructose induced low copper availability might be an important mechanism underlying fructose induced fatty liver.

Occurrence of the Transferable Copper Resistance Gene tcrB among Fecal Enterococci of U.S. Feedlot Cattle Fed Copper-Supplemented Diets

Copper, an essential micronutrient, is supplemented in the diet at elevated levels to reduce morbidity and mortality and to promote growth in feedlot cattle. Gut bacteria exposed to copper can acquire resistance, which among enterococci is conferred by a transferable copper resistance gene (tcrB) borne on a plasmid. The present study was undertaken to investigate whether the feeding of copper at levels sufficient to promote growth increases the prevalence of the tcrB gene among the fecal enterococci of feedlot cattle. The study was performed with 261 crossbred yearling heifers housed in 24 pens, with pens assigned randomly to a 2×2 factorial arrangement of treatments consisting of dietary copper and a commercial linseed meal-based energy protein supplement. A total of 22 isolates, each identified as Enterococcus faecium, were positive for tcrB with an overall prevalence of 3.8% (22/576). The prevalence was higher among the cattle fed diets supplemented with copper (6.9%) compared to normal copper levels (0.7%). The tcrB-positive isolates always contained both erm(B) and tet(M) genes. Median copper MICs for tcrB-positive and tcrB-negative enterococci were 22 and 4 mM, respectively. The transferability of the tcrB gene was demonstrated via a filter-mating assay. Multilocus variable number tandem repeat analysis revealed a genetically diverse population of enterococci. The finding of a strong association between the copper resistance gene and other antibiotic (tetracycline and tylosin) resistance determinants is significant because enterococci remain potential pathogens and have the propensity to transfer resistance genes to other bacteria in the gut.

Presenilin Promotes Dietary Copper Uptake

Dietary copper is essential for multicellular organisms. Copper is redox active and required as a cofactor for enzymes such as the antioxidant Superoxide Dismutase 1 (SOD1). Copper dyshomeostasis has been implicated in Alzheimer’s disease. Mutations in the presenilin genes encoding PS1 and PS2 are major causes of early-onset familial Alzheimer’s disease. PS1 and PS2 are required for efficient copper uptake in mammalian systems. Here we demonstrate a conserved role for presenilin in dietary copper uptake in the fly Drosophila melanogaster. Ubiquitous RNA interference-mediated knockdown of the single Drosophila presenilin (PSN) gene is lethal. However, PSN knockdown in the midgut produces viable flies. These flies have reduced copper levels and are more tolerant to excess dietary copper. Expression of a copper-responsive EYFP construct was also lower in the midgut of these larvae, indicative of reduced dietary copper uptake. SOD activity was reduced by midgut PSN knockdown, and these flies were sensitive to the superoxide-inducing chemical paraquat. These data support presenilin being needed for dietary copper uptake in the gut and so impacting on SOD activity and tolerance to oxidative stress. These results are consistent with previous studies of mammalian presenilins, supporting a conserved role for these proteins in mediating copper uptake.

Small Animal Review

Introduction Increased dietary copper availability may impact on the development of chronic hepatitis in Labrador Retrievers.

Does Dietary Copper Supplementation Enhance or Diminish PCB126 Toxicity in the Rodent Liver?

Copper is essential for the function of the mitochondrial electron transport chain and several antioxidant proteins. However, in its free form copper can participate in Fenton-like reactions that produce reactive hydroxyl radicals. Aryl-hydrocarbon receptor (AhR) agonists, including the most potent polychlorinated biphenyl (PCB) congener, 3,3',4,4',5-pentachlorobiphenyl (PCB126), increase copper levels in rodent livers. This is accompanied by biochemical and toxic changes. To assess the involvement of copper in PCB toxicity, male Sprague-Dawley rats were fed an AIN-93G diet with differing dietary copper levels: low (2 ppm), adequate (6 ppm), and high (10 ppm). After three weeks, rats from each group were given a single ip injection of corn oil (control), 1, or 5 μmol/kg body weight PCB126. Two weeks following injections, biochemical and morphological markers of hepatic toxicity, trace metal status, and hepatic gene expression of metalloproteins were evaluated. Increasing dietary copper was associated with elevated tissue levels of copper and ceruloplasmin. In the livers of PCB126-treated rats, the hallmark signs of AhR activation were present, including increased cytochrome P450 and lipid levels and decreased glutathione. In addition, a doubling of hepatic copper levels was seen, and overall metal homeostasis was disturbed, resulting in decreased hepatic selenium, manganese, zinc, and iron. Expression of key metalloproteins was either decreased (cytochrome c oxidase), unchanged (ceruloplasmin and CuZnSOD), or increased (tyrosinase and metallothioneins 1 and 2) with exposure to PCB126. Increases in metallothionein may contribute/reflect the increased copper seen. Alterations in dietary copper did not amplify or abrogate the hepatic toxicity of PCB126. PCB126 toxicity, i.e., oxidative stress and steatosis, is clearly associated with disturbed metal homeostasis. Understanding the mechanisms of this disturbance may provide tools to prevent liver toxicity by other AhR agonists.

Study of micronutrients (copper, zinc and vitamin B12) in posterolateral myelopathies

BackgroundVitamin B12 deficiency is a well recognized cause of posterolateral myelopathy. In Indian subcontinent, it may coexist with nutritional copper deficiency producing partial response of patients to B12 supplementation. Hence the study was planned to look for association of hypocupremia and B12 deficiency. MethodsTwenty-three patients with posterolateral myelopathy (Romberg sign positive) were enrolled and investigated for levels of vitamin B12, copper and zinc and followed up for six months. ResultIn three patients, copper deficiency alone was found to be the cause. In another three, both copper and vitamin B12 were deficient. In all these six patients, ceruloplasmin and 24h urinary copper were found to be low suggesting dietary copper deficiency. Hyperzincemia was found in four of these patients. Magnetic resonance imaging of spine was normal in lone Cu deficient patients but showed T2 hyperintensity of posterior column in lone B12 or combined B12 and copper deficiency. ConclusionIn cases of B12 deficiency myelopathy not responding to supplementation, copper deficiency must be sought at the earliest to avoid and treat persistent neurological disability.

Dietary copper supplementation restores β-cell function of Cohen diabetic rats: a link between mitochondrial function and glucose-stimulated insulin secretion

β-Cell mitochondrial dysfunction as well as proinflammatory cytokines have been suggested to contribute to reduced glucose-stimulated insulin secretion (GSIS) in type 2 diabetes. We recently demonstrated that Cohen diabetic sensitive (CDs) rats fed a high-sucrose, low-copper diet (HSD) developed hyperglycemia and reduced GSIS in association with peri-islet infiltration of fat and interleukin (IL)-1β-expressing macrophages, whereas CD resistant (CDr) rats remained normoglycemic on HSD. We examined: 1) the correlation between copper concentration in the HSD and progression, prevention, and reversion of hyperglycemia in CDs rats, 2) the relationship between activity of the copper-dependent, respiratory-chain enzyme cytochrome c oxidase (COX), infiltration of fat, IL-1β-expressing macrophages, and defective GSIS in hyperglycemic CDs rats. CDs and CDr rats were fed HSD or copper-supplemented HSD before and during hyperglycemia development. Blood glucose and insulin concentrations were measured during glucose tolerance tests. Macrophage infiltration and IL-1β expression were evaluated in pancreatic sections by electron-microscopy and immunostaining. COX activity was measured in pancreatic sections and isolated islets. In CDs rats fed HSD, GSIS and islet COX activity decreased, while blood glucose and infiltration of fat and IL-1β-expressing macrophages increased with time on HSD (P < 0.01 vs. CDr-HSD rats, all parameters, respectively). CDs rats maintained on copper-supplemented HSD did not develop hyperglycemia, and in hyperglycemic CDs rats, copper supplementation restored GSIS and COX activity, reversed hyperglycemia and infiltration of fat and IL-1β-expressing macrophages (P < 0.01 vs. hyperglycemic CDs-HSD rats, all parameters, respectively). We provide novel evidence for a critical role of low dietary copper in diminished GSIS of susceptible CDs rats involving the combined consequence of reduced islet COX activity and pancreatic low-grade inflammation.

The treatment of Wilson's disease, a rare genetic disorder of copper metabolism.

Wilson's disease is a rare autosomal recessive disease characterised by the deposition of copper in the brain, liver; cornea, and other organs. The overload of copper inevitably leads to progressive liver and neurological dysfunction. Copper overload in patients with Wilson's disease is caused by impairment to the biliary route for excretion of dietary copper A combination of neurological, psychiatric and hepatic symptoms can make the diagnosis of Wilson's disease challenging. Most symptoms appear in the second and third decades of life. The disease affects between one in 30,000 and one in 100,000 individuals, and is fatal if left untreated. Five drugs are currently available to treat Wilson's disease: British Anti-Lewisite; D-penicillamine; trientine; zinc sulfate or acetate; and ammonium tetrathiomolybdate. Each drug can reduce copper levels and/or transform copper into a metabolically inert and unavailable form in the patient. The discovery and introduction of these five drugs owes more to the inspiration of a few dedicated physicians and agricultural scientists than to the resources of the pharmaceutical industry.