Abstract  The toxicity of vanadium (Va) salts was determined in a variety of animals. The action of vanadium on the circulating blood cells was studied on rabbits. The distribution of Va in chronic and acute poisoning was determined. A careful macroscopic and microscopic examination was made of all animals poisoned by Va. Colloidal vanadium-pentoxide (1314621) and ammonium-metavanadate (7803556) were the most toxic salts while vanadyl-sulfate (27774136) and sodium-hexavanadate (12026083) were the least toxic compounds. Mice and rats were the most resistant to Va; rabbits and horses, the most sensitive. Va poisoning was dominated by two groups of symptoms which could develop simultaneously. One was the result of depression, and in severe intoxication, acute paralysis of the respiratory center. The other was due to pulmonary, kidney, and gastrointestinal lesions. The chief action of Va was exerted on the vascular system. In tolerated doses, Va had no influence on circulating blood. In chronic intoxication, the red cells were directly affected. The bone marrow sometimes showed an increase in the neutrophilic myelocytes, while the lymphoid elements were decreased. The authors conclude that the pathological changes characterize Va as a neurotoxic and a hemorrhagic endotheliotoxic poison with a hepatotoxic, nephrotoxic, and probably leukocytotoxic and hemotoxic component.

Abstract  Vanadium compounds have been shown to have insulin-like properties in rats and non-insulin-dependent diabetic humans. The purpose of the present study was to examine whether the effects of acute and short-term administration of vanadyl sulfate (VA) on insulin sensitivity also exist in healthy active individuals. Five male and two female participants (age: 24.9 +/- 1.5 years; height: 176.1 +/- 2.9 cm; body mass: 70.1 +/- 2.9 kg) underwent 3 oral glucose tolerance tests (OGTT). The first OGTT was performed to obtain a baseline index of insulin sensitivity (ISI). On the night preceding the second OGTT, participants ingested 100 mg of VS, and the acute effects of VS on ISI were examined. For the next 6 days, participants were instructed to ingest 50 mg of VS twice daily, and a final OGTT was performed on day 7 to determine the short-term effects of VS on ISI. No differences were found in fasting plasma glucose and insulin concentrations after VS administration. Furthermore, ISI after 1 day and 7 days of VS administration was not different compared with baseline ISI (4.8 +/- 0.1 vs. 4.7 +/- 0.1 vs. 4.7 +/- 0.1, respectively). These results demonstrate that there are no acute and short-term effects of VS administration on insulin sensitivity in healthy humans.

Abstract  The effects of 1 microgram/mL of vanadium, given for 12 mo as sodium metavanadate in drinking water, on cardiovascular and biochemical indices of male rabbits were investigated. At the end of the exposure period, vanadium was more accumulated in bones and kidneys than in spleen and liver; the cardiac ventricles and the aorta contained similar amounts of this element. Blood pressure and heart rate were unchanged in the vanadate-exposed animals since the observed decrease of both cardiac inotropism and stroke volume was counteracted by an increase of peripheral vascular resistance, with reduction of arterial blood flow. The arterial levels of sodium, potassium and aldosterone were unmodified by vanadate which, however, strongly raised those of noradrenaline, adrenaline, L-DOPA, and dopamine. Vanadate caused a marked increase of the activity of monoamine oxidase in renal tubules and liver (probably in relation to the increased plasma catecholamine levels) and a reduction of that of glucose-6-phosphate dehydrogenase in the kidney. There was also evidence that vanadium reduces synthesis and/or release of nitric oxide, the endothelium-derived vasodilating factor, likely through a reduced formation from bradykinin. It was concluded that vanadium may represent an environmental factor of altered cardiovascular homeostasis.

Abstract  We compared the effects of oral vanadyl sulfate (100 mg/day) in moderately obese NIDDM and nondiabetic subjects. Three-hour euglycemic-hyperinsulinemic (insulin infusion 30 mU / m / min) clamps were performed after 2 weeks of placebo and 3 weeks of vanadyl sulfate treatment in six nondiabetic control subjects (age 37 +/- 3 years; BMI 29.5 +/- 2.4 kg/m2 ) and seven NIDDM subjects (age 53 +/- 2 years; BMI 28.7 +/-1.8 kg/m2). Glucose turnover ([3-3 H]glucose), glycolysis from plasma glucose, glycogen synthesis, and whole-body carbohydrate and lipid oxidation were evaluated. Decreases in fasting plasma glucose (by approximately 1.7 mmol/l) and HbAlc (both P < 0.05) were observed in NIDDM subjects during treatment; plasma glucose was unchanged in control subjects. In the latter, the glucose infusion rate (GIR) required to maintain euglycemia (40.1 +/- 5.7 and 38.1 +/- 4.8 micromol / kg fat-free mass FFM / min) and glucose disposal (Rd) (41.7 +/- 5.7 and 38.9 +/-4.7 micromol / kg FFM / min were similar during placebo and vanadyl sulfate administration, respectively. Hepatic glucose output (HGO) was completely suppressed in both studies. In contrast, in NIDDM subjects, vanadyl sulfate increased GIR approximately 82% (17.3 +/- 4.7 to 30.9 +/- 2.7 micromol / kg FFM / min, P < 0.05); this improvement in insulin sensitivity was due to both augmented stimulation of Rd (26.0 +/-4.0 vs. 33.6 +/- 2.22 micromol / kg FFM / min, P < 0.05) and enhanced suppression of HGO (7.7 +/- 3.1 vs. 1.3 +/- 0.9 micromol / kg FFM / min, P < 0.05). Increased insulin-stimulated glycogen synthesis accounted for >80% of the increased Rd with vanadyl sulfate (P < 0.005), but plasma glucose flux via glycolysis was unchanged. In NIDDM subjects, vanadyl sulfate was also associated with greater suppression of plasma free fatty acids (FFAs) (P < 0.01) and lipid oxidation (P < 0.05) during clamps. The reduction in HGO and increase in Rd were both highly correlated with the decline in plasma FFA concentrations during the clamp period (P < 0.001). In conclusion, small oral doses of vanadyl sulfate do not alter insulin sensitivity in nondiabetic subjects, but it does improve both hepatic and skeletal muscle insulin sensitivity in NIDDM subjects in part by enhancing insulin's inhibitory effect on lipolysis. These data suggest that vanadyl sulfate may improve a defect in insulin signaling specific to NIDDM.