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

The effect of pervanadate, a potent insulinomimetic agent that inhibits insulin receptor dephosphorylation in vitro, is now assessed in vivo. A single i.p. administration of pervanadate at concentrations as low as 700 micrograms vanadium/kg body wt markedly lowered blood glucose levels in streptozotocin-induced diabetic rats from 430 +/- 28 to 212 +/- 30 mg/100 ml within 3 h. A decrease was already observed half hour after treatment, continued in accelerating fashion to the 3rd h, and persisted for at least 24 h. The initial hyperglycemia reoccurred on the second day and remained thereafter. In comparable fashion, pervanadate decreased the blood glucose levels of control healthy rats, treated identically. Within this period body wt was not significantly altered in either group. This data indicate that rapid and efficient management of glucose homeostasis is achieved via inhibiting receptor dephosphorylation. This observation may lead to a new therapeutic approach of protein tyrosine phosphatase inhibition for future treatment of diabetes in general, and in insulin resistant states in particular.
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PMID:The protein tyrosine phosphatase inhibitor, pervanadate, is a powerful antidiabetic agent in streptozotocin-treated diabetic rats. 827 68

To study the effect of vanadium (V) intake on blood glucose lowering, tissue V concentrations, glutathione reductase (GR) activity, and plasma trace metal concentrations, streptozotocin(STZ)-diabetic rats were treated with vanadyl sulfate (VS) (0.5-1.2 g/l in the drinking water) for up to 12 weeks. Kidney and plasma V concentrations were positively correlated with V intake. Kidney GR activities were not affected by VS treatment nor were plasma cobalt, molybdenum, manganese or lithium concentrations. Individual V intakes were dependent upon severity of diabetes, with more hyperglycemic rats consuming greater quantities of VS solution. A diminished effect on glucose lowering of VS above 1 g/l was noted.
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PMID:Studies of vanadyl sulfate as a glucose-lowering agent in STZ-diabetic rats. 828 Jan 74

It has been shown that improvement of glucose homeostasis by oral vanadate or vanadyl treatment in streptozotocin-induced diabetic rats is accompanied by severe negative side effects (some deaths, decreased weight gain, alteration in renal function as well as tissue vanadium accumulation) which argue against the use of vanadium compounds in diabetes treatment. The present study was undertaken to assess the effectiveness in alleviating some signs of diabetes in streptozotocin-treated rats with oral therapy with sodium metavanadate (NaVO3) and sodium 4,5 dihydroxybenzene-1,3-disulfonate (Tiron), a chelating agent effective in mobilizing vanadium. In a preliminary experiment, diabetic rats were given aqueous solutions of 0.20 mg NaVO3/ml for 4 days. Vanadium-treated rats which showed blood glucose levels significantly lower (p < 0.001) than vanadate-untreated diabetic rats were selected for subsequent experiments. These animals were given 0.20 mg NaVO3/ml in drinking water and 0, 125.6, 314 or 628 mg Tiron/kg/d by gavage for 2 w. Although most of the animals did not become normoglycemic, several characteristic signs of diabetes (hyperglycemia, hyperphagia and polydipsia) were alleviated by the NaVO3 treatment. The administration of 314 mg Tiron/kg/d (approximately 1 NaVO3: 5 Tiron, mole ratio) did not diminish the ameliorative effects of NaVO3 with respect to diabetes, but significantly decreased the level of vanadium accumulation in target organs. These results show that some of the beneficial effects of NaVO3 are maintained in diabetic animals given Tiron, while the administration of the chelator results in a significant decrease in tissue vanadium accumulation. Accordingly, this would diminish the possibility of toxic side effects derived from prolonged oral vanadium administration.
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PMID:Oral vanadate and Tiron in treatment of diabetes mellitus in rats: improvement of glucose homeostasis and negative side-effects. 830 15

The vanadyl (+IV) form of vanadium has been demonstrated to have insulin-mimetic activity in vivo. In an effort to improve the poor gastrointestinal absorption of the ion, an organic complex of vanadyl (naglivan) was synthesized. We tested the antidiabetic effects of naglivan in rats made diabetic with streptozotocin (55 mg/kg, i.v.). Four days after the streptozotocin injection, one diabetic group (DVI) and a control group (CV) were treated with naglivan (50 mg/kg/day, equivalent to 0.06 mmol vanadium/kg/day) by oral gavage. Treatment in the DVI group was supplemented with daily insulin while a second diabetic group (DI) was administered daily titrated doses of insulin alone (Protamine Zinc, s.c.) to achieve stable euglycemia. The dose of exogenous insulin required to maintain normal glucose was significantly lower in the DVI group compared to the DI throughout the treatment period. At the end of week 3, exogenous insulin was withdrawn from both the DVI and DI groups, while naglivan treatment was continued in the CV and DVI groups for an additional 5 weeks. At termination, hearts were isolated and cardiac function (+dP/dt, -dP/dt and left ventricular developed pressure) was assessed in all the animals. After insulin was withdrawn, 4/8 DVI animals which continued to receive naglivan had consistent normoglycemia (as determined by % glycosylated hemoglobin) and an improved cardiac function. All the DI animals and 4/8 DVI rats were hyperglycemic and had depressed heart function despite having similar plasma insulin levels to the euglycemic DVI animals. As with vanadyl sulfate, there were no signs of long-term toxicity with regards to renal or liver function after 8 weeks of treatment. Thus, naglivan is an orally effective form of vanadyl with an oral potency 7.6 times greater than that of vanadyl sulfate (minimum effective dose: 0.06 mmol vanadium.kg-1.day-1) as compared to vanadyl sulfate (0.46 mmol vanadium.kg-1.day-1). The lack of incidence of diarrhea in either control or diabetic animals demonstrates that naglivan could be a more therapeutically desirable form of vanadyl.
Diabetes Res Clin Pract 1993 May
PMID:In vivo antidiabetic actions of naglivan, an organic vanadyl compound in streptozotocin-induced diabetes. 837 71

The effects of oral vanadate supplementation on intestinal morphometry and glucose transport were examined in STZ-induced diabetic and age-matched control male Sprague-Dawley rats. Animals received 0.1 mg/ml vanadium pentoxide in their drinking water over 14 days. Vanadate reduced intestinal glucose maximal transport capacity in both diabetic and control animals. In jejunum tissue, this decrease in glucose absorption was a direct consequence of downregulation of the glucose carrier and was not related to changes in mucosal morphometry. In the ileum tissue of control animals, the vanadate-induced decrease in glucose maximal transport capacity occurred in conjunction with an increase in carrier affinity and mucosal morphometric measurements. In the ileum tissue of diabetic animals, the vanadate-induced decrease in glucose maximal transport capacity occurred with a decrease in mucosal morphometric measurements. Na(+)-K(+)-adenosine triphosphatase activity was affected by vanadate only in diabetic animals. These results demonstrate that oral vanadate supplementation results in downregulation of the small intestinal sodium-dependent glucose carrier in both diabetic and nondiabetic rats. Furthermore, the vanadate effect may be occurring at the cellular level.
Diabetes 1993 Aug
PMID:Oral vanadate reduces Na(+)-dependent glucose transport in rat small intestine. 839 10

Common metabolic problems in northeastern Thailand include renal stone disease, distal renal tubular acidosis, hypokalemic periodic paralysis, sudden unexplained nocturnal death and malnutrition-related diabetes mellitus. There is evidence of decreased activity of Na,K-ATPase and H,K-ATPase. A preliminary study was made of the vanadium concentration in the soil and water in northeastern Thailand. The urinary and tissue vanadium concentrations were also determined in the northeastern villagers. The soil was found to have high vanadium content. The vanadium content was also high in the urine, kidneys and lungs of the villagers. It is postulated that these metabolic problems are attributed to the inhibition of Na,K-ATPase and H,K-ATPase activity by vanadium.
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PMID:Metabolic problems in northeastern Thailand: possible role of vanadium. 839 62

Vanadium, a trace metal in the environment and in biological systems, influences the behavior of enzymes, mimics and regulates growth factor activity, is a potential mutagenic and carcinogenic agent, and regulates gene expression. The diverse biological actions of vanadium result from its capacity to function as an oxyanion, oxycation, or prooxidant. Vanadium is found in water, rocks, and soils in low concentration and in relatively high concentrations in coal and oil deposits. Vanadium compounds at much higher concentrations than are typically ingested are being considered in the treatment of diabetes mellitus. The actions of insulin and vanadium on the insulin receptor are similar, but the mechanisms are not identical. Vanadium modulates growth-factor-mediated signal transduction pathways. Vanadium promotes cell transformation and diminishes cell adhesion. Consistent with its mitogenic action and its capacity to mimic mitogenic growth factors, vanadium stimulates expression of protooncogenes. In particular, oxygen-derived active species are involved in the expression of the jun protooncogene in the presence of vanadium. The unique cellular activity of vanadium makes it a tool of unparalleled potential for studying mechanisms of cell growth, differentiation, and metabolism.
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PMID:Vanadium as a modulator of cellular regulatory cascades and oncogene expression. 839 67

Decreased cardiac function in streptozotocin-diabetic rats has been used as a model of diabetes-induced cardiomyopathy, which is a secondary complication in diabetic patients. The present study was designed to evaluate the therapeutic effect of a new organic vanadium complex, bis(maltolato)oxovanadium(IV), (BMOV), in improving heart function in streptozotocin-diabetic rats. There were four groups of male, Wistar rats: control (C), control treated (CT), diabetic (D), and diabetic treated (DT). Treatment consisted of BMOV, 0.5 mg/mL (1.8 mM) for the first 3 weeks and 0.75 mg/mL (2.4 mM) for the next 22 weeks, in the drinking water of rats allowed ad libitum access to food and water. BMOV lowered blood glucose to < 9 mM in 70% of DT animals without any increase in plasma insulin levels, and mean blood glucose and plasma lipid levels were significantly lower in DT vs. D rats. Tissue vanadium levels were measured in plasma, bone, kidney, liver, muscle, and fat of BMOV-treated rats. Plasma vanadium levels averaged 0.84 +/- 0.07 microgram/mL (16.8 microM) in CT rats and 0.76 +/- 0.05 microgram/mL (15.2 microM) in DT animals. The highest vanadium levels at termination of this chronic feeding study were in bone, 18.3 +/- 3.0 micrograms/g (0.37 mumol/g) in CT and 26.4 +/- 2.6 micrograms/g (0.53 mumol/g) in DT rats, with intermediate levels in kidney and liver, and low, but detectable levels in muscle and fat. There were no deaths in either the CT or DT group, and no overt signs of vanadium toxicity were present. Tissue vanadium levels were not correlated with the glucose-lowering effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improvement in cardiac dysfunction in streptozotocin-induced diabetic rats following chronic oral administration of bis(maltolato)oxovanadium(IV). 840 91

The trace element vanadium is a potent insulinomimetic agent in vitro. Oral administration of vanadate to rats made diabetic by streptozotocin (45 mg/kg i.v.) caused a 65% fall in plasma glucose levels without modifying low insulinemia. We studied whether the hypoglycemic effect of vanadate was associated with altered expression of genes involved in key steps of hepatic glucose metabolism. Glucokinase (GK) and L-type pyruvate kinase (L-PK) mRNA levels were decreased respectively by 90% and 70% in fed diabetic rats, in close correlation with changes in enzyme activities. Eighteen days of vanadate treatment partially restored GK mRNA and activity (40% of control levels), and totally restored L-PK parameters. In contrast to the glycolytic enzymes, mRNA levels and activity of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK) were increased (15- and 2-fold, respectively) in fed diabetic rats. Vanadate treatment normalized both PEPCK mRNA and activity in diabetic rat liver. The 2-fold increase in liver glucose transporter (GLUT2) mRNA and protein, produced by diabetes, was also corrected by this treatment. In conclusion, oral vanadate given to diabetic rats induces a shift of the predominating gluconeogenic flux, with subsequent high hepatic glucose production, into a glycolytic flux by pretranslational regulatory mechanisms.
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PMID:Vanadate treatment of diabetic rats reverses the impaired expression of genes involved in hepatic glucose metabolism: effects on glycolytic and gluconeogenic enzymes, and on glucose transporter GLUT2. 847 58

Having briefly analyzed the role of vanadium in living organisms, the author describes conditions induced by vanadium poisoning and deficit. The most recent acquisitions concerning the use of vanadium in the treatment of diabetes mellitus and its consequent role in the prevention of atherosclerosis are also illustrated.
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PMID:[Vanadium, an indispensable trace element in living organisms. Current data on biochemical, metabolic levels and therapeutic doses]. 848 65


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