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

The PI-3 kinase signalling pathway is an important pathway in mediating the glucoregulatory effects of insulin and skeletal muscle (SKM) is the major tissue involved in glucose utilization. In diabetes this pathway is impaired, either due to lack of insulin as in Type I diabetes, or due to insulin resistance as in Type 2 diabetes. Bis(maltolato)-oxovanadium IV (BMOV), an insulin mimetic/enhancing agent, produces a marked glucose lowering effect in models of both types of diabetes. Some in vitro studies have shown that phosphatidylinositol 3 kinase (PI-3 kinase) activity is enhanced by vanadium. In the present study we looked at changes in PI-3 kinase expression and activity in SKM from STZ-diabetic and fa/fa Zucker rats treated with BMOV for 3 weeks. Although BMOV treatment completely normalized glucose levels in STZ-diabetic rats, no effect was observed on basal or insulin-stimulated PI-3 kinase activity. In fatty Zucker rats, activation of PI-3 kinase activity after insulin injection was impaired as compared to age matched lean controls, but BMOV again did not affect the activity. These results suggest that although PI-3 kinase is an important signalling factor in glucose utilization, vanadium treatment does not reduce hyperglycemia through activation of SKM PI-3 kinase in vivo.
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PMID:In vivo effects of vanadium in diabetic rats are independent of changes in PI-3 kinase activity in skeletal muscle. 1168 10

Recent studies have shown that vanadium salts are able to reduce blood glucose in diabetics and overcome, to some degree, insulin resistance. This paradigm has been followed to monitor the effects of diabetes and vanadyl treatment on brain calcineurin (CN), an important protein phosphatase. Male rats were rendered diabetic by a single injection of streptozotocin (STZ), resulting in an elevation of blood glucose from 108 +/- 13 to >400 mg/dl. Diabetic animals were given vanadyl sulfate trihydrate (0.5 mg/dl.) in their drinking water for 3 weeks, which led to a fall in blood glucose to 156 +/- 53 mg/ml. Brain CN activity (units/mg brain protein) in diabetic rats was 77% that of control animals, whereas vanadyl-treated diabetic animals were characterized by CN activities like that of controls. CN was purified from brains of control animals, STZ-induced diabetic animals, and STZ-induced diabetic animals receiving vanadyl, then spin-labeled with 3-maleimide-proxyl and studied via electron spin resonance spectroscopy. The rotational correlation time of CN from control animals and vanadyl-treated diabetic animals was 6.4 x 10(-11) s(-1), whereas that from STZ-induced-diabetic animals was 8 x 10(-11) s(-1). Thus, STZ-induced diabetes in rats results in an increase in the rotational correlation time of brain CN relative to control animals, yet vanadyl treatment of STZ-induced diabetic animals reduced the rotational correlation time to that of control. These data suggest that diabetes can lead to apparent conformational changes in brain CN; also, CN conformation in diabetic rats was restored by vanadyl treatment.
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PMID:Conformation changes in brain calcineurin in diabetic rats with or without treatment with vanadyl sulfate. 1175 5

Vanadium is an element classified in the group of heavy metals, very common in the natural environment and widely used in industry. It is mainly used in the production of nonferrous alloys, most resistant carbon steel, as well as in chemical, glass, paint and varnish, ceramic, and photographic industries. In the atmosphere, two second of vanadium originates from anthropogenic sources, sea-born aerosols and volcanic eruptions. Municipal waste is the major source of vanadium in surface water. It is one of the components of live organisms and participates in many biochemical processes essential for their proper functioning, but in higher concentrations it may induce acute or chronic intoxication that damage biological structures and disorder biochemical systems. The mechanism of vanadium toxic effect has not as yet been elucidated, however, it is already known that this mechanism is rooted among others in vanadium properties able to hinder a number of enzymatic systems. For vanadium the most "critical" systems are respiratory, urinary and hemopoietic. Vanadium salts may also be genotoxic and harmful at different phases of reproduction and development. Numerous studies of a possible use of vanadium in treatment of certain diseases, e.g., diabetes, have been carried out. Some findings on a potential antineoplastic or contraceptive effect of vanadium compounds have recently been reported. To sum up, there are numerous hazards associated with the wide industrial use of vanadium, nevertheless, the number of findings highlighting its nutritive and therapeutic properties is growing.
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PMID:[Vanadium: threat and hope]. 1176 61

In vivo effects of insulin and vanadium treatment on glycogen synthase (GS), glycogen synthase kinase-3 (GSK-3) and protein phosphatase-1 (PP1) activity were determined in Wistar rats with streptozotocin (STZ)-induced diabetes. The skeletal muscle was freeze-clamped before or following an insulin injection (5 U/kg i.v.). Diabetes, vanadium, and insulin in vivo treatment did not affect muscle GSK-3beta activity as compared to controls. Following insulin stimulation in 4-week STZ-diabetic rats muscle GS fractional activity (GSFA) was increased 3 fold (p < 0.05), while in 7-week diabetic rats it remained unchanged, suggesting development of insulin resistance in longer term diabetes. Muscle PP1 activity was increased in diabetic rats and returned to normal after vanadium treatment, while muscle GSFA remained unchanged. Therefore, it is possible that PP1 is involved in the regulation of some other cellular events of vanadium (other than regulation of glycogen synthesis). The lack of effect of vanadium treatment in stimulating glycogen synthesis in skeletal muscle suggests the involvement of other metabolic pathways in the observed glucoregulatory effect of vanadium.
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PMID:Effects of diabetes, vanadium, and insulin on glycogen synthase activation in Wistar rats. 1195 62

Today, vanadium compounds are frequently included in nutritional supplements and are also being developed for therapeutic use in diabetes mellitus. Previously, tissue uptake of vanadium from bis(maltolato)oxovanadium(IV) (BMOV) was shown to be increased compared to its uptake from vanadyl sulfate (VS). Our primary objective was to test the hypothesis that complexation increases vanadium uptake and that this effect is independent of oxidation state. A secondary objective was to compare the effects of vanadium complexation and oxidation state on tissue iron, copper, and zinc. Wistar rats were fed either ammonium metavanadate (AMV), VS, or BMOV (1.2 mM each in the drinking water). Tissue uptake of V following 12 wk of BMOV or AMV was higher than that from VS (p < 0.05). BMOV led to decreased tissue Zn and increased bone Fe content. The same three compounds were compared in a cellular model of absorption (Caco-2 cells). Vanadium uptake from VS was higher than that from BMOV or AMV at 10 min, but from BMOV (250 microM only, 60 min), uptake was far greater than from AMV or VS. These results show that neither complexation nor oxidation state alone are adequate predictors of relative absorption, tissue accumulation, or trace element interactions.
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PMID:Influence of chelation and oxidation state on vanadium bioavailability, and their effects on tissue concentrations of zinc, copper, and iron. 1200 58

In the 21st century, patients suffering from diabetes mellitus (DM), a lifestyle-related disease, will increase more than in the 20th century. DM is threatening because of the development of many severe secondary complications, including atherosclerosis, microangiopathy, renal dysfunction and failure, cardiac abnormalities, diabetic retinopathy, and ocular disorders. Generally, DM is classified as either insulin-dependent type 1 or noninsulin-dependent type 2 DM. Type 1 DM is treated only by daily insulin injections; type 2 DM is treated by several types of synthetic therapeutic substances together with a controlled diet and physical exercise. Even with these measures, the daily necessity for several insulin injections can be painful both physically and mentally, whereas the synthetic therapeutic substances used over the long term often have side effects. For those reasons, the creation and development of a new class of pharmaceuticals for treatment of DM in the 21st century would be extremely desirable. In the last half of the 20th century, investigations of the relationships among diseases and micronutrients, such as iron, copper, zinc, and selenium, have been numerous. Research into the development of metallopharmaceuticals involving the platinum-containing anticancer drug, cisplatin, and the gold-containing rheumatoid arthritis drug, auranofin, has also been widespread. Such important findings prompted us to develop therapeutic reagents based on a new concept to replace either insulin injections or the use of synthetic drugs. After many trials, we noticed that vanadium might be very useful in the treatment of DM. Before the discovery of insulin by Banting and Best in 1921 and its clinical trial for treating DM, the findings in 1899, in which orally administered sodium vanadate (NaVO(3)) was reported to improve human DM, gave us the idea to use vanadium to treat DM. However, it has taken a long time to obtain a scientific explanation as to why the metal ion exhibits insulin-mimetic or blood-glucose lowering effects in in vitro and in vivo experiments. After investigations from many perspectives involving biochemistry and bioinorganic chemistry, vanadyl sulfate (VOSO(4)) and its complexes with several types of ligands have been proposed as useful for treating DM in experimental diabetic animals. On the basis of a mechanistic study, this article reports on recent progress regarding the development of antidiabetic vanadyl complexes, emphasizing that the vanadyl ion and its complexes are effective not only in treating or relieving both types of DM but also in preventing the onset of DM.
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PMID:A new concept: the use of vanadium complexes in the treatment of diabetes mellitus. 1220 6

Tungstate is an oxyanion that has biological similarities to vanadate. In recent years, a number of studies have shown the antidiabetic effects of oral tungstate in animal models of diabetes. However, because of the tissue accumulation and potential toxicity derived from chronic administration of vanadium and tungsten compounds, the pharmacological use of vanadate or tungstate in the treatment of diabetes is not necessarily exempt from concern. In the context of a potential use in the treatment of human diabetes mellitus, the most relevant toxic effects of vanadium derivatives are reviewed and compared with those reported for tungsten. Hematological and biochemical alterations, loss of body weight, nephrotoxicity, immunotoxicity, reproductive and developmental toxicity, and behavioral toxicity have been reported to occur following exposure to vanadium compounds. Moreover, vanadium also has a mitogenic activity affecting the distribution of chromosomes during mitosis and inducing aneuploidy-related end points. In contrast to vanadate, studies about the toxic effects of tungstate are very scant. Early investigations in cats, rabbits, dogs, mice, and rats showed that tungstate was less toxic than vanadate when given intravenously. Although in vitro investigations showed a direct effect of tungstate on the embryo and fetus of mice at concentrations similar to those causing effects in vivo, information on the potential cellular toxicity of tungstate is particularly scarce. Taking into account the recent interest of tungstate as a new potential oral antidiabetic agent, an exhaustive evaluation of its toxicity in mammals is clearly necessary.
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PMID:Vanadium and tungsten derivatives as antidiabetic agents: a review of their toxic effects. 1229 30

Among the previously studied organic vanadium derivatives showing an anti-diabetic action, we investigated a new complex, bis(2,2'-bipyridine)oxovanadium(IV) sulphate. We tested its ability to normalise parameters previously described for streptozotocin (STZ)-diabetes, such as lower yields of Golgi-rich membrane fraction isolation, decreased activity of Golgi membrane marker enzyme - galactosyltransferase (GalT) - and altered morphology of rat liver Golgi complexes. Oral application as a drinking solution of 1.8 mmol bis(2,2'-bipyridine)oxovanadium(IV) (dissolved in 0.09 M NaCl) caused a similar dispersion of GalT activities in both vanadium treated groups, control and diabetic. Very low activities of the enzyme (characteristic for untreated diabetes) we found only in approximately 35 % of the STZ-diabetic rats treated with the new vanadium compound. The morphology of liver Golgi complexes in diabetic rats treated with bis(2,2'-bipyridine)oxovanadium(IV) sulphate was improved, which manifested itself in the reappearance of vacuoles with VLDL and coated and uncoated secretory vesicles. In view of biochemical and morphological parameters of normalised diabetic rat liver Golgi apparatus, the new vanadium complex was more effective than bis(oxalato)oxovanadium(IV) or bis(kojato)oxovanadium(IV), but in our experimental model, the best anti-diabetic, orally applied drug was the bis(maltolato)oxovanadium(IV) previously investigated.
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PMID:The influence of a new vanadium compound, bis(2,2'-bipyridine)oxovanadium(IV) sulphate on liver golgi complexes from control and streptozotocin-diabetic rats. 1243 83

Identification of a vanadium compound with the highest efficacy and least toxicity is the main scientific problem in diabetes treatment. All vanadium complexes, both inorganic and organic, apart from improving physiological and biochemical diabetic parameters, show more or less toxic effects in living organisms. For this reason we decided to test a new vanadium compound: bis(2,2'-bipyridine)oxovanadium(IV), [VO(bpy)2], not used or described so far. This paper stressed morphological alterations of rat liver Golgi apparatus originated from control or streptozotocin (STZ)-diabetic rats treated with 1.8 mmol VO(bpy)2 solution in 0.5% NaCl as drinking liquid for 7 days and compared them with a parallel biochemical study. There was a correlation between the activity of Golgi marker enzyme i.e. galactosyl transferase and morphology of this organelle. In control rats treatment with VO(bpy)2 caused drastic changes, in many cases leading to a complete destruction of liver Golgi apparatus. In STZ-diabetic liver of rats treated with VO(bpy)2 the Golgi apparatus showed characteristic of untreated diabetes arching or even twisting of stack cisternae but improvement of the secretory activity (dilatation of cisternae edges, some secretory vacuoles and vesicles). In our opinion, the parallel action of two drugs: STZ combined with VO(bpy)2, relieves or even eliminate harmful effects of each compound alone.
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PMID:Control and STZ-diabetic rat liver Golgi complexes under the influence of bis(2,2'-bipyridine)oxovanadium(IV) sulphate. The morphological investigation. 1247 13

The activity of galactosyltransferase (GalT), the Golgi apparatus marker enzyme, together with the morphology of this organelle in rat liver, are so characteristic that we have used them for twenty years as a test of streptozotocin-diabetes, and of the efficacy of different drugs. Bis(maltolato)oxovanadium(IV) (BMOV), an oral vanadium complex with anti-diabetic properties, best of these drugs, was seen to reverse the previously found biochemical and morphological changes. Four groups of diabetic rats were studied in different conditions: 1) untreated diabetes (D group), 2) pre-treatment with BMOV for two days, to accustom the animals to the taste of vanadium solution and to verify possible cytoprotection of the drug, followed by the induction of diabetes c. 3 weeks later (pVD group). The third group--3) consisted of the rats, in which STZ-diabetes was induced followed by treatment of diabetic animals with 1.8 mmol BMOV in 0.5% NaCl for seven days (D+V group). The fourth group--4) consisted of the animals treated as pVD group, followed by induction of diabetes three weeks later and treatment with BMOV (pVD+V group) for seven days. In agreement with other investigators, the reduction of body weight was seen in all diabetic rats. Vanadium treatment caused the greatest body weight reduction. Liquid and food intake was lower in both groups at seven days after treatment with BMOV. Major biochemical alterations in yields of Golgi-rich membrane fraction were found in D, pVD and pVD+V groups. They were significantly lower (p < 0.01) than in D+V group. A significantly lower activity of GalT (total activity and calculated in nmol transferred per h and per g of liver) was found in the three groups of diabetic rats in comparison with D+V group (p < 0.01 or p < 0.001). GalT activities, as well as the yield of Golgi fraction in D+V group, were similar to the previously obtained in control or control vanadium treated groups. A major morphological alteration was observed in D and pVD+V groups (characteristic semicircular or arched Golgi apparatus--AG). In the pVD group a different structure of AG was seen: short terminally dilated cisternae, sometimes only semicircular and arched. In rats treated 7 days with BMOV (the D+V group) the "normalisation" of morphology of liver AG was noted.
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PMID:The influence of BMOV [bis(maltolato)oxovanadium(IV)] on biochemical and morphological alterations characteristic for streptozotocin-diabetic rat liver Golgi complexes. 1259 38


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