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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperglycemia portends chronic complications in insulin-dependent diabetes mellitus (IDDM) and substantial benefits are associated with "tight" glycemic control. Other interventions should either enhance glycemic control per se or add benefit to an established degree of glycemic control. Several micronutrients enhance insulin action and others offer promise in countering the untoward consequences of hyperglycemia. Supplements of micronutrients including the vitamins niacin (as niacinamide), C and E and the minerals zinc, chromium and vanadium have been studied. For the purpose of this review, the term "nutriceutic" refers to supplementation on the order of 2 to 10 times the RDA for which a benefit is linked to a mechanism of action. Benefits associated with "nutriceutic" supplementation are reported in small trials for vitamins C and E and these supplements are safe and affordable from food or tablet sources. A dietary strategy adding 200-600 mg of vitamin C and 100 IU of vitamin E to a healthy dietary pattern is worthy of consideration as an intervention for individuals with IDDM.
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PMID:Micronutrients as nutriceutical interventions in diabetes mellitus. 947 83

A growing body of experimental and clinical research indicates that the trace element, vanadium, exerts potent insulin-mimetic effects in vitro and in vivo when used in pharmacological doses. Since our first demonstration of the anti-diabetic and cardioprotective effects of vanadium in vivo, impressive advances have been made in our understanding of its mechanism of action, pharmacokinetics and pharmacodynamics. A major advance in the use of vanadium as an insulin-mimetic has been the development of organic vanadium complexes which are 2 to 3 times as potent as inorganic vanadium and have been extensively studied in our laboratory. There is an emerging role for the use of vanadium in human diabetes and the recently conducted clinical trials support this contention. The present review summarizes some of the key aspects of vanadium biology which exemplify the potent insulin-mimetic, anti-diabetic and antihypertensive effects of this intriguing trace element.
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PMID:Nutritional factors that can favorably influence the glucose/insulin system: vanadium. 947 84

Salts of the trace element vanadium, such as sodium orthovanadate and vanadyl sulfate (VS), exhibit a myriad of insulin-like effects, including stimulation of glycogen synthesis and improvement of glucose homeostasis in type I and type II animal models of diabetes mellitus. However, the cellular mechanism by which these effects are mediated remains poorly characterized. We have shown earlier that different vanadium salts stimulate the MAP kinase pathway and ribosomal-S-6-kinase (p70s6k) in chinese hamster ovary cells overexpressing human insulin receptor (CHO-HIR cells) [Pandey, S. K., Chiasson, J.-L., and Srivastava, A. K. (1995) Mol. Cell. Biochem. 153, 69-78]. In the present studies, we have investigated if similar to insulin, VS also activates phosphatidylinositol 3-kinase (PI3-k) activity, and whether VS-induced activation of the PI3-k, MAP kinase, and p70s6k pathways contributes to glycogen synthesis. Treatment of CHO-HIR cells with VS resulted in increased glycogen synthesis and PI3-k activity which were blocked by pretreatment of the cells with wortmannin and LY294002, two specific inhibitors of PI3-k. On the other hand, PD98059 and rapamycin, specific inhibitors of the MAP kinase pathway and p70s6k, respectively, were unable to inhibit VS-stimulated glycogen synthesis. Moreover, VS-stimulated glycogen synthesis and PI3-k were observed without any change in the tyrosine phosphorylation of insulin receptor (IR) beta-subunit but were associated with increased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation.
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PMID:Vanadyl sulfate-stimulated glycogen synthesis is associated with activation of phosphatidylinositol 3-kinase and is independent of insulin receptor tyrosine phosphorylation. 957 88

The pathophysiologic importance of insulin resistance in diseases such as obesity and diabetes mellitus has led to great interest in defining the mechanism of insulin action as well as the means to overcome the biochemical defects responsible for the resistance. Vanadium compounds have been discovered to mimic many of the metabolic actions of insulin both in vitro and in vivo and improve glycemic control in human subjects with diabetes mellitus. Apart from its direct insulinmimetic actions, we found that vanadate modulates insulin metabolic effects by enhancing insulin sensitivity and prolonging insulin action. All of these actions appear to be related to protein tyrosine phosphatase (PTP) inhibition. However, in contrast to its stimulatory effects, vanadate inhibits basal and insulin-stimulated system A amino acid uptake and cell proliferation. The mechanism of these actions also appears to be related to PTP inhibition, consistent with the multiple roles of PTPs in regulating signal transduction. While the precise biochemical pathway of vanadate action is not yet known, it is clearly different from that of insulin in that the insulin receptor and phosphatidylinositol 3'-kinase do not seem to be essential for vanadate stimulation of glucose uptake and metabolism. The ability of vanadium compounds to 'bypass' defects in insulin action in diseases characterized by insulin resistance and their apparent preferential metabolic versus mitogenic signaling profile make them attractive as potential pharmacological agents.
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PMID:Multifunctional actions of vanadium compounds on insulin signaling pathways: evidence for preferential enhancement of metabolic versus mitogenic effects. 960 20

The progress of knowledge relating to non-insulin-dependent diabetes mellitus (NIDDM) is associated with new therapeutic developments. Their different respective targets allow to classify them in drugs stimulating insulin secretion (glimepiride, repaglinide, glucagon-like peptide 1), medications reducing insulin resistance (thiazolidinediones) or in insulinmimetic agents (vanadium). Alpha glucosidase inhibitors, available in France since 1993, constitute another therapeutic approach, reducing postprandial hyperglycemia by delaying the digestion of complex carbohydrates. These new medications, safer and sometimes effective in a single daily administration, represent an alternative to classic oral antidiabetic agents allowing therapeutic combinations and a more global management of NIDDM.
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PMID:[New therapies in type 2 diabetes]. 978 90

The relation between bis(maltolato)oxovanadium(IV) (BMOV) influencing the biochemical activity of rat liver Golgi apparatus and the morphology of this organelle was studied in normal and streptozotocin-diabetic rat livers. Ultrastructural examinations revealed marked differences in the morphology of Golgi apparatus in three groups of animals. In the control rats treated only with 0.5% NaCl we did not find any biochemical and morphological changes. Marked changes were found in the rat liver after 1.8 mmol BMOV in 0.5% NaCl (as drinking solution) applied for 7 days, so-called "control" group for vanadium. In this group Golgi apparatus seemed shorter than in the diabetic animals. Finally, the same treatment of rats with previously induced SZ-diabetes, showed relatively small morphological alterations. The ultrastructural observation was compatible with the activity of galactosyltransferase (GalT), the Golgi marker enzyme. In diabetic rats treated with BMOV the activity of this enzyme was almost the same as in controls. Summing up dramatic alterations, previously found in diabetic-untreated rats [22], normalized after orally applied BMOV solution, even after a short time.
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PMID:Influence of bis(maltolato)oxovanadium(IV) on activity of galactosyltransferase (GalT) and morphology of rat liver Golgi apparatus in control and streptozotocin diabetes. 979 9

We demonstrated in 1985 that vanadium administered in the drinking water to streptozotocin (STZ) diabetic rats restored elevated blood glucose to normal. Subsequent studies have shown that vanadyl sulfate can lower elevated blood glucose, cholesterol and triglycerides in a variety of diabetic models including the STZ diabetic rat, the Zucker fatty rat and the Zucker diabetic fatty rat. Long-term studies of up to one year did not show toxicity in control or STZ rats administered vanadyl sulfate in doses that lowered elevated blood glucose. In the BB diabetic rat, a model of insulin-dependent diabetes, vanadyl sulfate lowered the insulin requirement by up to 75%. Vanadyl sulfate is effective orally when administered by either single dose or chronic doses. It is also effective by the intraperitoneal route. We have also been able to demonstrate marked long-term effects of vanadyl sulfate in diabetic animals following treatment and withdrawal of vanadyl sulfate. Because vanadyl sulfate is not well absorbed we have synthesized and tested a number of organic vanadium compounds. One of these, bismaltolato-oxovanadium IV (BMOV), has shown promise as a therapeutic agent. BMOV is 2-3x more potent than vanadyl sulfate and has shown less toxicity. Recent studies from our laboratory have shown that the effects of vanadium are not due to a decrease in food intake and that while vanadium is deposited in bone it does not appear to affect bone strength or architecture. The mechanism of action of vanadium is currently under investigation. Several studies indicate that vanadium is a phosphatase inhibitor and that vanadium can activate serine/threonine kinases distal to the insulin receptor presumably by preventing dephosphorylation due to inhibition of phosphatases Short-term clinical trials using inorganic vanadium compounds in diabetic patients have been promising.
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PMID:Vanadium and diabetes. 1093 42

The element vanadium can have insulin mimetic properties and therefore has been suggested as a possible therapeutic agent for treatment of diabetes. A series of peroxovanadium compounds that are more potent at lowering blood glucose levels than sodium metavanadate, sodium orthovanadate and vanadyl sulfate have recently been synthesized. These compounds probably will not be orally active so transdermal administration is a potential option. A patch containing either the peroxovanadium compound [VO(O2)2 1-10 phenanthroline], abbreviated bpV(phen), or placebo was placed on the back of streptozotocin induced diabetic rats and was delivered either passively (16 h) or iontophoretically (0.5 mA/cm2 for 4 h). Blood samples were analyzed for glucose and vanadium levels. Mean blood glucose levels were 83+/-1% and 109+/-1% of the starting values for animals iontophoretically treated with bpV(phen) and vehicle, respectively. The compound's insulin mimetic properties were evident within 60 min of current initiation. Blood glucose levels were reduced to 74+/-14% of the original level after 16 h of passive treatment. The compound was ineffective when fed to animals. Transdermal delivery of bpV(phen) resulted in significantly greater blood levels of vanadium than the orally delivered compound (P<0.05). Overall these experiments demonstrate that peroxovanadium delivered through the skin can lower blood glucose levels in rats. Further experiments are warranted to better characterize the nature of the response and to determine the potential for using these compounds in humans.
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PMID:Transdermally delivered peroxovanadium can lower blood glucose levels in diabetic rats. 1036 Nov 62

The potential role of vanadium in human health is described as a building material of bones and teeth. However, another very interesting and promising application for vanadium in human health emerges from recent studies that evaluated the role of vanadium in the management of diabetes. Vanadium is present in a variety of foods that we commonly eat. Skim milk, lobster, vegetable oils, many vegetables, grains and cereals are rich source of vanadium (>1 ppm). Fruits, meats, fish, butter, cheese, and beverages are relatively poor sources of vanadium. The daily dietary intake in humans has been estimated to vary from 10 microg to 2 mg of elemental vanadium, depending on the environmental sources of this mineral in the air, water, and food of the particular region tested. In animals, vanadium has been shown essential (1-10 microg vanadium per gram of diet). There is only circumstantial evidence that vanadium is essential for humans. However, in doses ranging from 0.083 mmol/d to 0.42 mmol/d, vanadium has shown therapeutic potential in clinical studies with patients of both insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) type. Although vanadium has a significant biological potential, it has a poor therapeutic index, and attempts have been made to reduce the dose of vanadium required for therapeutic effectiveness. Organic forms of vanadium, as opposed to the inorganic sulfate salt of vanadium, are recognized as safer, more absorbable, and able to deliver a therapeutic effect up to 50% greater than the inorganic forms. The goal is to provide vanadium with better gastrointestinal absorption, and in a form that is best able to produce the desired biological effects. As a result, numerous organic complexes of vanadium have been developed including bis(maltolato)oxovanadium (BMOV), bis(cysteinamide N-octyl)oxovanadium known as Naglivan, bis(pyrrolidine-N-carbodithioato)oxovanadium, vanadyl-cysteine methyl ester, and bis-glycinato oxovanadium (BGOV). The health benefits of vanadium and the safety and efficacy of the available vanadium supplements are discussed in this review.
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PMID:Vanadium: a review of its potential role in the fight against diabetes. 1038 Dec 52

Vanadium compounds, at much higher concentrations than they are typically ingested, are being considered for use in the treatment of diabetes mellitus. They exert an insulin-mimetic effect in an insulin-receptor-independent manner. In our study we obtained new data about the vanadium insulin-receptor-independent mechanism of action on cell membranes. When rat stomach smooth muscle samples are treated with NH4VO3 (10(-7) divided by 10(-5) this action is possibly exhibited with increased influx of Ca2+ through VDCa2+C.
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PMID:Possible mechanism of action of vanadium ions as an antidiabetic agent. 1046 17


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