Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arsenic concentrations were determined in 126 urine samples by hydride generation atomic absorption spectrometry. Samples were mineralized with nitric acid in a thermostated mineralization block. This technique was compared with a method that involves mineralization in a microwave digestion bomb. A mean recovery percentage of 100.80 +/- 5.57% was obtained. The relative standard deviation ranged from 1.7 to 10.52%. It was found that subject sex and age did not affect urine As levels (P > 0.05). The mean urine As levels in patients with hepatic injury (4.24 +/- 1.98 micrograms/l), diabetes (3.44 +/- 2.36 micrograms/l) and myocardial infarction (3.64 +/- 1.85 micrograms/l) were not statistically different (P > 0.05) to that found in the control group (healthy subjects) (3.68 +/- 2.27 micrograms/l). This result could be related to the fact that the regulation of As in the human organism is independent of these diseases. Measured As concentrations in the eight basic health zones of the study area were not statistically different (P > 0.01). This fact demonstrates the existence of a similarly low environmental As distribution in coastal and mountainous zones.
 ...
PMID:Urine arsenic concentrations in healthy adults as indicators of environmental contamination: relation with some pathologies. 961 28

The objective of this study was to assess whether arsenic exposure is a risk factor for diabetes mellitus as indicated in a few earlier studies. Arsenic in drinking water is known to occur in western Bangladesh, and in 1996, two of the authors conducted a survey of the prevalence of diabetes mellitus among 163 subjects with keratosis taken as exposed to arsenic and 854 unexposed individuals. Diabetes mellitus was determined by history of symptoms, previously diagnosed diabetes, glucosuria, and blood sugar level after glucose intake. The crude prevalence ratio for diabetes mellitus among keratotic subjects exposed to arsenic was 4.4 (95% confidence interval 2.5-7.7) and increased to 5.2 (95% confidence interval 2.5-10.5) after adjustment for age, sex, and body mass index. On the basis of a few earlier measurements of arsenic concentrations in drinking water by the authorities in Bangladesh and another 20 new ad hoc analyses, approximate time-weighted exposure levels to arsenic in drinking water could be estimated for each subject. Three time-weighted average exposure categories were created, i.e., less than 0.5, 0.5-1.0, and more than 1.0 mg/liter. For the unexposed subjects, the corresponding prevalence ratios were 1.0, 2.6, 3.9, and 8.8, representing a significant trend in risk (p < 0.001). The result corroborates earlier studies and suggests that arsenic exposure is a risk factor for diabetes mellitus.
 ...
PMID:Diabetes mellitus associated with arsenic exposure in Bangladesh. 967 2

There is evidence indicating that ingestion of arsenic may predispose the development of diabetes mellitus in arsenic-endemic areas in Taiwan. However, the prevalence of diabetes and related vascular diseases in the entire southwestern arseniasis-endemic and nonendemic areas remains to be elucidated. We used the National Health Insurance Database for 1999-2000 to derive the prevalence of non-insulin-dependent diabetes and related vascular diseases by age and sex among residents in southwestern arseniasis-endemic and nonendemic areas in Taiwan. The study included 66,667 residents living in endemic areas and 639,667 in nonendemic areas, all greater than or equal to 25 years of age. The status of diabetes and vascular diseases was ascertained through disease diagnosis and treatment prescription included in the reimbursement claims of clinics and hospitals. The prevalence of non-insulin-dependent diabetes, age- and gender-adjusted to the general population in Taiwan, was 7.5% (95% confidence interval, 7.4-7.7%) in the arseniasis-endemic areas and 3.5% (3.5-3.6%) in the nonendemic areas. Among both diabetics and nondiabetics, higher prevalence of microvascular and macrovascular diseases was observed in arseniasis-endemic than in the nonendemic areas. Age- and gender-adjusted prevalence of microvascular disease in endemic and nonendemic areas was 20.0% and 6.0%, respectively, for diabetics, and 8.6% and 1.0%, respectively, for nondiabetics. The corresponding prevalence of macrovascular disease was 25.3% and 13.7% for diabetics, and 12.3% and 5.5% for nondiabetics. Arsenic has been suggested to increase the risk of non-insulin-dependent diabetes mellitus and its related micro- and macrovascular diseases.
 ...
PMID:Prevalence of non-insulin-dependent diabetes mellitus and related vascular diseases in southwestern arseniasis-endemic and nonendemic areas in Taiwan. 1257 98

Arsenic is a carcinogen to both humans and animals. Arsenicals have been associated with cancers of the skin, lung, and bladder. Clinical manifestations of chronic arsenic poisoning include non-cancer end point of hyper- and hypo-pigmentation, keratosis, hypertension, cardiovascular diseases and diabetes. Epidemiological evidence indicates that arsenic concentration exceeding 50 microg l(-1) in the drinking water is not public health protective. The current WHO recommended guideline value for arsenic in drinking water is 10 microg l(-1), whereas many developing countries are still having a value of 50 microg l(-1). It has been estimated that tens of millions of people are at risk exposing to excessive levels of arsenic from both contaminated water and arsenic-bearing coal from natural sources. The global health implication and possible intervention strategies were also discussed in this review article.
 ...
PMID:A global health problem caused by arsenic from natural sources. 1286 64

Arsenic and arsenic containing compounds are human carcinogens. Exposure to arsenic occurs occupationally in several industries, including mining, pesticide, pharmaceutical, glass and microelectronics, as well as environmentally from both industrial and natural sources. Inhalation is the principal route of arsenic exposure in occupational settings, while ingestion of contaminated drinking water is the predominant source of significant environmental exposure globally. Drinking water contamination by arsenic remains a major public health problem. Acute and chronic arsenic exposure via drinking water has been reported in many countries of the world, where a large proportion of drinking water is contaminated with high concentrations of arsenic. General health effects that are associated with arsenic exposure include cardiovascular and peripheral vascular disease, developmental anomalies, neurologic and neurobehavioural disorders, diabetes, hearing loss, portal fibrosis, hematologic disorders (anemia, leukopenia and eosinophilia) and multiple cancers: significantly higher standardized mortality rates and cumulative mortality rates for cancers of the skin, lung, liver, urinary bladder, kidney, and colon in many areas of arsenic pollution. Although several epidemiological studies have documented the sources of exposure and the global impact of arsenic contamination, the mechanisms by which arsenic induces health effects, including cancer, are not well characterized. Further research is needed to provide a better understanding of the pathobiology of arsenic-induced diseases and to better define the toxicologic pathology of arsenic in various organ systems. In this review, we provide and discuss the underlying pathology and nature of arsenic-induced lesions. Such information is critical for understanding the magnitude of health effects associated with arsenic exposure throughout the world.
 ...
PMID:Carcinogenic and systemic health effects associated with arsenic exposure--a critical review. 1458 26

Arsenic is a naturally occurring element, but anthropogenic activities can lead to a substantial contamination of the environment. Exposure to arsenic has been associated with a significant number of adverse health effects in humans including: cardiovascular disease, diabetes, hearing loss, developmental abnormalities, anemia, neurologic and neurobehavioral disorder, leukopenia, eosinophilia, fibrosis of the liver and the kidney and various neoplasms. However, the cellular and molecular events associated with arsenic toxicity are poorly understood. Also, the precise mechanisms by which arsenic acts as a carcinogen in humans remain to be elucidated. In the present study, we used human liver carcinoma (HepG2) cells as a model to study the molecular mechanisms of arsenic-induced toxicity and carcinogenesis. We hypothesized that arsenic-induced expression of stress genes and related proteins may play a role in the cellular and molecular events leading to toxicity and tumorigenesis in liver cells. To test this hypothesis, we performed the MTT-assay for cell viability, the CAT-Tox (L) assay for gene induction, and the Western Blot analysis to assess the expression of cellular proteins including c-fos, HMTIIA, HSP70 and p53. Data obtained from the MTT assay indicated a strong dose-response relationship with respect to arsenic trioxide toxicity. Upon 48 hr of exposure, the chemical dose required to cause 50% reduction in cell viability (LD50) was computed to be 8.55 +/- 0.58 microg/ml. The CAT-Tox (L) assay showed statistically significant inductions (p<0.05) of c-fos, HMTIIA, and HSP70. Western blot analysis also demonstrated a dose-response relationship with regard to expression of specific cellular proteins. The p53 protein was expressed in arsenic trioxide-treated cells, however, the densitometric analysis did not show any significant differences (p<0.05) between treated and control cells. The lack of a significant induction of p53 may be due to the potential mitogenic effect of arsenic at low levels of arsenic exposure.
 ...
PMID:Arsenic trioxide-induced transcriptional activation of stress genes and expression of related proteins in human liver carcinoma cells (HepG2). 1468 89

Chronic arsenic exposure is associated with an increased risk for cancer, cardiovascular disease (including ischemic heart disease and hypertension), peripheral vascular disease, and diabetes. Arsenic causes blood vessel growth and remodeling in vivo and cell specific, dose-dependent induction vascular endothelial growth factor-A (VEGF), which is essential for both processes. The current study examined the hypothesis that low, environmentally relevant levels of trivalent arsenic (AsIII) activate discrete signaling pathways in vascular smooth muscle cells (SMC) to induce expression of VEGF. AsIII caused a progressive increase in VEGF mRNA levels over a 48 h period in primary porcine SMC with a threshold of 1-2.5 microM. VEGF protein levels increased with a similar concentration dependence and time course. Hypoxia inducible factor-1alpha (HIF-1alpha) protein and mRNA levels also increased in response to AsIII. However, unlike the response to an iron chelator, AsIII-induced VEGF was not inhibited by siRNA directed toward HIF-1alpha. Instead, a novel protein kinase C, PKCdelta, was activated by AsIII to induce VEGF and stabilize HIF-1alpha. Consistent with this activation, AsIII caused coordinate increases in the levels of the intracellular second messenger diacyglycerol (DAG). These data suggest that AsIII induced divergent signaling pathways in SMCs that lead to independent increases in VEGF expression and HIF-1alpha signaling. However, these pathways both require initial increases in DAG levels and PKC activity.
 ...
PMID:Signaling pathways for arsenic-stimulated vascular endothelial growth factor-a expression in primary vascular smooth muscle cells. 1508 98

Arsenic (As) contamination of drinking water is considered a principal environmental health threat throughout the world. Chronic intake is associated with an increased risk of cancer, diabetes, and cardiovascular disease, and recent studies suggest increased health risks at levels as low as 5-10 ppb. We report here that 0.05-1 microM (6-120 ppb) As showed stimulatory effects on glucocorticoid receptor (GR)-mediated gene activation in rat EDR3 hepatoma cells of both the endogenous tyrosine aminotransferase (TAT) gene and the reporter genes containing TAT glucocorticoid response elements. At slightly higher concentrations (1-3 microM), the effects of As became inhibitory. Thus, over this narrow concentration range, the effects of As changed from a 2- to 4-fold stimulation to a greater than 2-fold suppression in activity. Interestingly, the inhibitory effect of GR on both AP1- and NF-kappa B-mediated gene activation was not affected by As. The magnitude of GR stimulation and inhibition by As was highly dependent on the cellular level of hormone-activated GR. Mutational deletion studies indicated that the central DNA binding domain (DBD) of GR is the minimal region required for the As effect and does not require free sulfhydryls. Point mutations located within the DBD that have known structural consequences significantly altered the GR response to As. In particular, point mutations in the DBD that confer a DNA-bound GR confirmation abolished the low dose As stimulatory effect but enhanced the inhibitory response, further indicating that the DBD is important for mediating these As effects.
 ...
PMID:Arsenic at very low concentrations alters glucocorticoid receptor (GR)-mediated gene activation but not GR-mediated gene repression: complex dose-response effects are closely correlated with levels of activated GR and require a functional GR DNA binding domain. 1531 Feb 38

Metal-induced toxicity and carcinogenicity, with an emphasis on the generation and role of reactive oxygen and nitrogen species, is reviewed. Metal-mediated formation of free radicals causes various modifications to DNA bases, enhanced lipid peroxidation, and altered calcium and sulfhydryl homeostasis. Lipid peroxides, formed by the attack of radicals on polyunsaturated fatty acid residues of phospholipids, can further react with redox metals finally producing mutagenic and carcinogenic malondialdehyde, 4-hydroxynonenal and other exocyclic DNA adducts (etheno and/or propano adducts). Whilst iron (Fe), copper (Cu), chromium (Cr), vanadium (V) and cobalt (Co) undergo redox-cycling reactions, for a second group of metals, mercury (Hg), cadmium (Cd) and nickel (Ni), the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. Arsenic (As) is thought to bind directly to critical thiols, however, other mechanisms, involving formation of hydrogen peroxide under physiological conditions, have been proposed. The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. Common mechanisms involving the Fenton reaction, generation of the superoxide radical and the hydroxyl radical appear to be involved for iron, copper, chromium, vanadium and cobalt primarily associated with mitochondria, microsomes and peroxisomes. However, a recent discovery that the upper limit of "free pools" of copper is far less than a single atom per cell casts serious doubt on the in vivo role of copper in Fenton-like generation of free radicals. Nitric oxide (NO) seems to be involved in arsenite-induced DNA damage and pyrimidine excision inhibition. Various studies have confirmed that metals activate signalling pathways and the carcinogenic effect of metals has been related to activation of mainly redox-sensitive transcription factors, involving NF-kappaB, AP-1 and p53. Antioxidants (both enzymatic and non-enzymatic) provide protection against deleterious metal-mediated free radical attacks. Vitamin E and melatonin can prevent the majority of metal-mediated (iron, copper, cadmium) damage both in vitro systems and in metal-loaded animals. Toxicity studies involving chromium have shown that the protective effect of vitamin E against lipid peroxidation may be associated rather with the level of non-enzymatic antioxidants than the activity of enzymatic antioxidants. However, a very recent epidemiological study has shown that a daily intake of vitamin E of more than 400 IU increases the risk of death and should be avoided. While previous studies have proposed a deleterious pro-oxidant effect of vitamin C (ascorbate) in the presence of iron (or copper), recent results have shown that even in the presence of redox-active iron (or copper) and hydrogen peroxide, ascorbate acts as an antioxidant that prevents lipid peroxidation and does not promote protein oxidation in humans in vitro. Experimental results have also shown a link between vanadium and oxidative stress in the etiology of diabetes. The impact of zinc (Zn) on the immune system, the ability of zinc to act as an antioxidant in order to reduce oxidative stress and the neuroprotective and neurodegenerative role of zinc (and copper) in the etiology of Alzheimer's disease is also discussed. This review summarizes recent findings in the metal-induced formation of free radicals and the role of oxidative stress in the carcinogenicity and toxicity of metals.
 ...
PMID:Metals, toxicity and oxidative stress. 1589 31

Arsenic exposure is associated with hypertension, diabetes, and cancer. Some mammals methylate arsenic. Saccharomyces cerevisiae hexose permeases catalyze As(OH)(3) uptake. Here, we report that mammalian glucose transporter GLUT1 catalyzes As(OH)(3) and CH(3)As(OH)(2) uptake in yeast or in Xenopus laevis oocytes. Expression of GLUT1 in a yeast lacking other glucose transporters allows for growth on glucose. Yeast expressing yeast HXT1 or rat GLUT1 transport As(OH)(3) and CH(3)As(OH)(2). The K(m) of GLUT1 is to 1.2mM for CH(3)As(OH)(2), compared to a K(m) of 3mM for glucose. Inhibition between glucose and CH(3)As(OH)(2) is noncompetitive, suggesting differences between the translocation pathways of hexoses and arsenicals. Both human and rat GLUT1 catalyze uptake of both As(OH)(3) and CH(3)As(OH)(2) in oocytes. Thus GLUT1 may be a major pathway uptake of both inorganic and methylated arsenicals in erythrocytes or the epithelial cells of the blood-brain barrier, contributing to arsenic-related cardiovascular problems and neurotoxicity.
 ...
PMID:Mammalian glucose permease GLUT1 facilitates transport of arsenic trioxide and methylarsonous acid. 1706 64


1 2 3 4 5 6 7 8 9 Next >>