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Sevim Tunali - One of the best experts on this subject based on the ideXlab platform.
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ameliorative effect of vanadium on oxidative stress in stomach tissue of diabetic rats
Bosnian Journal of Basic Medical Sciences, 2014Co-Authors: Tugba Yilmazozden, Ozlem Kurtsirin, Sevim Tunali, Nuriye Akev, Refiye YanardagAbstract:Between their broad spectrum of action, vanadium compounds are shown to have insulin mimetic/enhancing effects. Increasing evidence in experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of diabetes and on the onset of diabetic complications. Thus, preventive therapy can alleviate the possible side effects of the disease. The aim of the present study was to investigate the effect of Vanadyl Sulfate supplementation on the antioxidant system in the stomach tissue of diabetic rats. Male Swiss albino rats were randomly divided into 4 groups: control; control+Vanadyl Sulfate; diabetic; diabetic+Vanadyl Sulfate. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body weight). Vanadyl Sulfate (100 mg/kg body weight) was given daily by gavage for 60 days. At the last day of the experiment, stomach tissues were taken and homogenized to make a 10% (w/v) homogenate. Catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), myeloperoxidase (MPO), carbonic anhydrase (CA), glucose-6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LDH) activities were determined in the stomach tissue. CAT, SOD, GR, GPx, GST, CA, G6PD and LDH activities were increased in diabetic rats when compared to normal rats. Vanadium treatment significantly reduced the elevated activities of GR, GPx, GST compared with the diabetic group whereas the decreases in CAT, SOD, CA, G6PD and LDH activities were insignificant. No significant change was seen for MPO activity between the groups. It was concluded that vanadium could be used for its ameliorative effect against oxidative stress in diabetes.
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protective effect of Vanadyl Sulfate on skin injury in streptozotocin induced diabetic rats
Human & Experimental Toxicology, 2013Co-Authors: Sevim Tunali, Refiye YanardagAbstract:The aim of the present study was to investigate the effect of Vanadyl Sulfate supplementation on the skin tissues of diabetic and control rats. In this study, 6–6.5 months old male Swiss albino rats were used. The animals were randomly divided into the following four groups: group I, control (nondiabetic intact animals); group II, Vanadyl Sulfate control; group III, streptozotocin (STZ)-diabetic animals and group IV, STZ-diabetic animals given Vanadyl Sulfate. The animals were made diabetic by intraperitoneal injection of a single dose of 65 mg/kg STZ in 0.01 M citrate buffer (pH = 4.5). From day 1 to day 60, 100 mg/kg Vanadyl Sulfate was given daily by gavage technique to one of the control and diabetic groups. Body weights and blood glucose levels were estimated on experimental days 0, 1 and 60. On the 60th day, skin tissue samples were taken, glutathione (GSH), lipid peroxidation (LPO), nonenzymatic glycosylation (NEG) and protein levels, catalase (CAT), superoxide dismutase (SOD) and glutathione-S-tra...
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Vanadyl Sulfate protects against streptozotocin induced morphological and biochemical changes in rat aorta
Cell Biochemistry and Function, 2007Co-Authors: Kadriye Akgundar, Sehnaz Bolkent, Refiye Yanardag, Sevim TunaliAbstract:The aim of this study was to investigate the protective effects of Vanadyl Sulfate on aorta tissue of normal and streptozotocin (STZ)-induced diabetic rats, morphologically and biochemically. The animals were made diabetic by an intraperitoneal injection of streptozotocin (65 mg/kg) and Vanadyl Sulfate (100 mg/kg) that was given every day for 60 days by gavage technique to rats. Under the light and transmission electron microscopes, hypertrophy of the vessel wall, focal disruption in the elastic lamellae, an increase in thickness of total aortic wall, tunica intima, subendothelial space and adventitial layer, and a disorganization in smooth muscular cells of the tunica media were observed in diabetic animals. The aorta lipid peroxidation (LPO) levels were significantly increased and the aorta glutathione (GSH) levels were significantly reduced in STZ diabetic rats. In diabetic rats administered Vanadyl Sulfate for 60 days, aorta LPO levels significantly decreased and the aorta GSH level significantly increased. In conclusion, in vivo treatment with Vanadyl Sulfate of diabetic rats prevented the morphological and biochemical changes observed in thoracic aorta of diabetic animals. Copyright © 2006 John Wiley & Sons, Ltd.
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Vanadyl Sulfate administration protects the streptozotocin induced oxidative damage to brain tissue in rats
Molecular and Cellular Biochemistry, 2006Co-Authors: Refiye Yanardag, Sevim TunaliAbstract:Diabetes mellitus manifests itself in a wide variety of complications and the symptoms of the disease are multifactorial. The present study was carried out to investigate the effects of Vanadyl Sulfate on biochemical parameters, enzyme activities and brain lipid peroxidation, glutathione and nonenzymatic glycosylation of normal- and streptozotocin-diabetic rats. Streptozotocin (STZ) was administered as a single dose (65 mg/kg) to induce diabetes. A dose of 100 mg/kg Vanadyl Sulfate was orally administered daily to STZ-diabetic and normal rats, separately until the end of the experiment, at day 60. In STZ-diabetic group, blood glucose, serum sialic and uric acid levels, serum catalase (CAT) and lactate dehydrogenase (LDH) activities, brain lipid peroxidation (LPO) and nonenzymatic glycosylation (NEG) increased, while brain glutathione (GSH) level and body weight decreased. In the diabetic group given Vanadyl Sulfate, blood glucose, serum sialic and uric acid levels, serum CAT and LDH activities and brain LPO and NEG levels decreased, but brain GSH and body weight increased.The present study showed that Vanadyl Sulfate exerted antioxidant effects and consequently may prevent brain damage caused by streptozotocin-induced diabetes.
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effect of Vanadyl Sulfate on the status of lipid parameters and on stomach and spleen tissues of streptozotocin induced diabetic rats
Pharmacological Research, 2006Co-Authors: Sevim Tunali, Refiye YanardagAbstract:Abstract Diabetes mellitus is a significant risk factor for cardiovascular complications. Experimental evidence suggests that oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. This study was undertaken to investigate the effect of Vanadyl Sulfate on blood glucose, serum and tissue lipid profiles and on stomach and spleen tissues in STZ-induced diabetic rats. In this study, male 6–6.5-month-old Swiss albino rats were used. Rats were randomly divided into four groups. Group I: control animals (normal, nondiabetic animals) ( n = 13); Group II: Vanadyl Sulfate controls ( n = 5); Group III: streptozotocin (STZ)–diabetic, untreated animals ( n = 11); and Group IV: STZ diabetic animals given Vanadyl Sulfate ( n = 11). Experimental diabetes was induced by intraperitoneal (i.p.) injection of STZ in a single dose of 65 mg kg −1 body weight. Vanadyl Sulfate was administered by gavage at a dose of 100 mg kg −1 . The levels of cholesterol, phospholipid, high density lipoprotein-cholesterol (HDL-), low density lipoprotein-cholesterol (LDL-), very low density lipoprotein-cholesterol (VLDL-), triglycerides and lipid peroxidation (LPO) in serum and cholesterol in liver were assayed according to standard procedures. The levels of lipid peroxidation, glutathione (GSH) and nonenzymatic glycosylation (NEG) in stomach and lipid peroxidation and glutathione (GSH) in spleen tissues were analyzed. After 60 days of treatment, serum cholesterol, LDL-cholesterol, triglyceride, phospholipid, VLDL-cholesterol, LPO, blood glucose levels, stomach LPO and NEG, spleen LPO significantly increased, but serum HDL-cholesterol, stomach GSH and spleen GSH levels significantly decreased in the diabetic group. On the other hand, treatment with Vanadyl Sulfate reversed these effects. These results reveal that diabetes mellitus increased oxidative damage in stomach and spleen tissues and Vanadyl Sulfate has an ameliorating effect on the oxidative stress via its antioxidant property. The administration of Vanadyl Sulfate may be able to reduce hyperglycemia and hyperlipidemia related to the risk of diabetes mellitus.
Refiye Yanardag - One of the best experts on this subject based on the ideXlab platform.
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ameliorative effect of vanadium on oxidative stress in stomach tissue of diabetic rats
Bosnian Journal of Basic Medical Sciences, 2014Co-Authors: Tugba Yilmazozden, Ozlem Kurtsirin, Sevim Tunali, Nuriye Akev, Refiye YanardagAbstract:Between their broad spectrum of action, vanadium compounds are shown to have insulin mimetic/enhancing effects. Increasing evidence in experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of diabetes and on the onset of diabetic complications. Thus, preventive therapy can alleviate the possible side effects of the disease. The aim of the present study was to investigate the effect of Vanadyl Sulfate supplementation on the antioxidant system in the stomach tissue of diabetic rats. Male Swiss albino rats were randomly divided into 4 groups: control; control+Vanadyl Sulfate; diabetic; diabetic+Vanadyl Sulfate. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body weight). Vanadyl Sulfate (100 mg/kg body weight) was given daily by gavage for 60 days. At the last day of the experiment, stomach tissues were taken and homogenized to make a 10% (w/v) homogenate. Catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), myeloperoxidase (MPO), carbonic anhydrase (CA), glucose-6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LDH) activities were determined in the stomach tissue. CAT, SOD, GR, GPx, GST, CA, G6PD and LDH activities were increased in diabetic rats when compared to normal rats. Vanadium treatment significantly reduced the elevated activities of GR, GPx, GST compared with the diabetic group whereas the decreases in CAT, SOD, CA, G6PD and LDH activities were insignificant. No significant change was seen for MPO activity between the groups. It was concluded that vanadium could be used for its ameliorative effect against oxidative stress in diabetes.
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protective effect of Vanadyl Sulfate on skin injury in streptozotocin induced diabetic rats
Human & Experimental Toxicology, 2013Co-Authors: Sevim Tunali, Refiye YanardagAbstract:The aim of the present study was to investigate the effect of Vanadyl Sulfate supplementation on the skin tissues of diabetic and control rats. In this study, 6–6.5 months old male Swiss albino rats were used. The animals were randomly divided into the following four groups: group I, control (nondiabetic intact animals); group II, Vanadyl Sulfate control; group III, streptozotocin (STZ)-diabetic animals and group IV, STZ-diabetic animals given Vanadyl Sulfate. The animals were made diabetic by intraperitoneal injection of a single dose of 65 mg/kg STZ in 0.01 M citrate buffer (pH = 4.5). From day 1 to day 60, 100 mg/kg Vanadyl Sulfate was given daily by gavage technique to one of the control and diabetic groups. Body weights and blood glucose levels were estimated on experimental days 0, 1 and 60. On the 60th day, skin tissue samples were taken, glutathione (GSH), lipid peroxidation (LPO), nonenzymatic glycosylation (NEG) and protein levels, catalase (CAT), superoxide dismutase (SOD) and glutathione-S-tra...
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Vanadyl Sulfate protects against streptozotocin induced morphological and biochemical changes in rat aorta
Cell Biochemistry and Function, 2007Co-Authors: Kadriye Akgundar, Sehnaz Bolkent, Refiye Yanardag, Sevim TunaliAbstract:The aim of this study was to investigate the protective effects of Vanadyl Sulfate on aorta tissue of normal and streptozotocin (STZ)-induced diabetic rats, morphologically and biochemically. The animals were made diabetic by an intraperitoneal injection of streptozotocin (65 mg/kg) and Vanadyl Sulfate (100 mg/kg) that was given every day for 60 days by gavage technique to rats. Under the light and transmission electron microscopes, hypertrophy of the vessel wall, focal disruption in the elastic lamellae, an increase in thickness of total aortic wall, tunica intima, subendothelial space and adventitial layer, and a disorganization in smooth muscular cells of the tunica media were observed in diabetic animals. The aorta lipid peroxidation (LPO) levels were significantly increased and the aorta glutathione (GSH) levels were significantly reduced in STZ diabetic rats. In diabetic rats administered Vanadyl Sulfate for 60 days, aorta LPO levels significantly decreased and the aorta GSH level significantly increased. In conclusion, in vivo treatment with Vanadyl Sulfate of diabetic rats prevented the morphological and biochemical changes observed in thoracic aorta of diabetic animals. Copyright © 2006 John Wiley & Sons, Ltd.
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Vanadyl Sulfate administration protects the streptozotocin induced oxidative damage to brain tissue in rats
Molecular and Cellular Biochemistry, 2006Co-Authors: Refiye Yanardag, Sevim TunaliAbstract:Diabetes mellitus manifests itself in a wide variety of complications and the symptoms of the disease are multifactorial. The present study was carried out to investigate the effects of Vanadyl Sulfate on biochemical parameters, enzyme activities and brain lipid peroxidation, glutathione and nonenzymatic glycosylation of normal- and streptozotocin-diabetic rats. Streptozotocin (STZ) was administered as a single dose (65 mg/kg) to induce diabetes. A dose of 100 mg/kg Vanadyl Sulfate was orally administered daily to STZ-diabetic and normal rats, separately until the end of the experiment, at day 60. In STZ-diabetic group, blood glucose, serum sialic and uric acid levels, serum catalase (CAT) and lactate dehydrogenase (LDH) activities, brain lipid peroxidation (LPO) and nonenzymatic glycosylation (NEG) increased, while brain glutathione (GSH) level and body weight decreased. In the diabetic group given Vanadyl Sulfate, blood glucose, serum sialic and uric acid levels, serum CAT and LDH activities and brain LPO and NEG levels decreased, but brain GSH and body weight increased.The present study showed that Vanadyl Sulfate exerted antioxidant effects and consequently may prevent brain damage caused by streptozotocin-induced diabetes.
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effect of Vanadyl Sulfate on the status of lipid parameters and on stomach and spleen tissues of streptozotocin induced diabetic rats
Pharmacological Research, 2006Co-Authors: Sevim Tunali, Refiye YanardagAbstract:Abstract Diabetes mellitus is a significant risk factor for cardiovascular complications. Experimental evidence suggests that oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. This study was undertaken to investigate the effect of Vanadyl Sulfate on blood glucose, serum and tissue lipid profiles and on stomach and spleen tissues in STZ-induced diabetic rats. In this study, male 6–6.5-month-old Swiss albino rats were used. Rats were randomly divided into four groups. Group I: control animals (normal, nondiabetic animals) ( n = 13); Group II: Vanadyl Sulfate controls ( n = 5); Group III: streptozotocin (STZ)–diabetic, untreated animals ( n = 11); and Group IV: STZ diabetic animals given Vanadyl Sulfate ( n = 11). Experimental diabetes was induced by intraperitoneal (i.p.) injection of STZ in a single dose of 65 mg kg −1 body weight. Vanadyl Sulfate was administered by gavage at a dose of 100 mg kg −1 . The levels of cholesterol, phospholipid, high density lipoprotein-cholesterol (HDL-), low density lipoprotein-cholesterol (LDL-), very low density lipoprotein-cholesterol (VLDL-), triglycerides and lipid peroxidation (LPO) in serum and cholesterol in liver were assayed according to standard procedures. The levels of lipid peroxidation, glutathione (GSH) and nonenzymatic glycosylation (NEG) in stomach and lipid peroxidation and glutathione (GSH) in spleen tissues were analyzed. After 60 days of treatment, serum cholesterol, LDL-cholesterol, triglyceride, phospholipid, VLDL-cholesterol, LPO, blood glucose levels, stomach LPO and NEG, spleen LPO significantly increased, but serum HDL-cholesterol, stomach GSH and spleen GSH levels significantly decreased in the diabetic group. On the other hand, treatment with Vanadyl Sulfate reversed these effects. These results reveal that diabetes mellitus increased oxidative damage in stomach and spleen tissues and Vanadyl Sulfate has an ameliorating effect on the oxidative stress via its antioxidant property. The administration of Vanadyl Sulfate may be able to reduce hyperglycemia and hyperlipidemia related to the risk of diabetes mellitus.
Melahat Dirican - One of the best experts on this subject based on the ideXlab platform.
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Vanadyl Sulfate taurine and combined Vanadyl Sulfate and taurine treatments in diabetic rats effects on the oxidative and antioxidative systems
Archives of Medical Research, 2007Co-Authors: Sibel Tas, Emre Sarandol, Zehra Serdar, Sedef Ziyanok Ayvalik, Melahat DiricanAbstract:Background Vanadyl Sulfate (VS) and taurine are two promising agents in the treatment of diabetes related to their antihyperglycemic, antihyperlipidemic, and hyperinsulinemic effects. Data about the effects of VS on the oxidant–antioxidant system is limited and controversial. However, taurine is a well-documented antioxidant agent and our aim was to investigate the effects of VS, taurine and VS and taurine combination on the oxidative–antioxidative systems in streptozotocin–nicotinamide (STZ-NA) diabetic rats. Methods Nicotinamide (230 mg/kg, i.p.) and streptozotocin (65 mg/kg, i.p.) were administered. VS (0.75 mg/mL) and taurine (1%) were added to drinking water for 5 weeks. Rats were divided as control (C), diabetes (D), diabetes + VS (D + VS), diabetes + taurine (D + T), diabetes + VS and taurine (D + VST). Plasma and tissue malondialdehyde (MDA) levels were measured by high-performance liquid chromatography and spectrophotometry, respectively. Paraoxonase and arylesterase activities were measured by spectrophotometric methods and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined using commercial kits. Results VS, taurine and VS and taurine combination treatments reduced the enhanced blood glucose, serum total cholesterol and triglyceride, tissue MDA and plasma MDA (except in the D + VS group) levels and increased the reduced serum insulin level, serum paraoxonase and arylesterase activities, GSH-Px activity and SOD activity (except in the D + VS group). Conclusions The findings of the present study suggest that VS and taurine exert beneficial effects on the blood glucose and lipid levels in STZ-NA diabetic rats. However, VS might exert prooxidative or antioxidative effects in various components of the body and taurine and VS combination might be an alternative for sole VS administration.
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Vanadyl Sulfate treatment improves oxidative stress and increases serum paraoxonase activity in streptozotocin induced diabetic rats
Nutrition Research, 2006Co-Authors: Sibel Tas, Emre Sarandol, Sedef Ziyanokayvalik, Nihal Ocak, Zehra Serdar, Melahat DiricanAbstract:Vanadyl Sulfate (VS) may reduce oxidative stress related to its hypoglycemic and hypolipidemic effects in diabetes mellitus; besides, as a catalytic element, it may induce lipid peroxidation. Studies investigating effects of VS on the oxidative-antioxidative systems in diabetes yielded conflicting results, and this study was designed to investigate the effects of VS on the oxidative-antioxidative systems in streptozotocin-induced (65 mg/kg) diabetic rats. Vanadyl Sulfate was administered in drinking water 0.75 mg/mL during 5 weeks after the induction of diabetes. Thirty-two male Wistar rats were randomly divided into four groups: control (C), control + Vanadyl Sulfate (C + VS), diabetes (D), and diabetes + Vanadyl Sulfate (D + VS). Vanadyl Sulfate reduced the enhanced glucose, lipid, and tissue malondialdehyde levels and increased the reduced serum paraoxonase and arylesterase activity in the D + VS group. Plasma malondialdehyde level was significantly increased in the C + VS group, compared with the control group. Erythrocyte glutathione peroxidase activity was significantly higher in the C + VS and D + VS groups, compared with the C and the D groups, respectively.The results of the present study suggest that (i) VS has antioxidative potential in streptozotocin-treated rats, and it might be used as a supportive therapeutic agent in uncontrolled diabetes; (ii) VS treatment might play a role in the improvement of serum paraoxonase activity and, thus, inhibit the progression of atherosclerosis; (iii) the prooxidant potential of the VS should be taken into account.
Min Wang - One of the best experts on this subject based on the ideXlab platform.
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Vanadyl Sulfate a simple catalyst for oxidation of alcohols with molecular oxygen in combination with 2 2 6 6 tetramethyl piperidyl 1 oxyl
Catalysis Communications, 2010Co-Authors: Min Wang, Yizheng HuangAbstract:Abstract Inexpensive Vanadyl Sulfate was developed in combination with 2,2,6,6-tetramethyl-piperidyl-1-oxyl (TEMPO) for catalytic oxidation of alcohols with molecular oxygen. A wide range of alcohols were oxidized to the corresponding carbonyl compounds in good conversions under mild conditions. No ligands or extra bases were used. Acetonitrile was the suitable solvent to keep the high activity of this system.
Allison B Goldfine - One of the best experts on this subject based on the ideXlab platform.
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coordination chemistry may explain pharmacokinetics and clinical response of Vanadyl Sulfate in type 2 diabetic patients
Metallomics, 2013Co-Authors: Gail R Willsky, Allison B Goldfine, Katherine Halvorsen, Michael E Godzala, Laihar Chi, Mathew J Most, Peter M Kaszynski, Debbie C Crans, Paul J KostyniakAbstract:Vanadium, abbreviated V, is an early transition metal that readily forms coordination complexes with a variety of biological products such as proteins, metabolites, membranes and other structures. The formation of coordination complexes stabilizes metal ions, which in turn impacts the biodistribution of the metal. To understand the biodistribution of V, V in oxidation state iv in the form of Vanadyl Sulfate (25, 50, 100 mg V daily) was given orally for 6 weeks to 16 persons with type 2 diabetes. Elemental V was determined using Graphite Furnas Atomic Absorption Spectrometry against known concentrations of V in serum, blood or urine. Peak serum V levels were 15.4 ± 6.5, 81.7 ± 40 and 319 ± 268 ng ml(-1) respectively, and mean peak serum V was positively correlated with dose administered (r = 0.992, p = 0.079), although large inter-individual variability was found. Total serum V concentration distribution fit a one compartment open model with a first order rate constant for excretion with mean half times of 4.7 ± 1.6 days and 4.6 ± 2.5 days for the 50 and 100 mg V dose groups respectively. At steady state, 24 hour urinary V output was 0.18 ± 0.24 and 0.97 ± 0.84 mg in the 50 and 100 mg V groups respectively, consistent with absorption of 1 percent or less of the administered dose. Peak V in blood and serum were positively correlated (r = 0.971, p < 0.0005). The serum to blood V ratio for the patients receiving 100 mg V was 1.7 ± 0.45. Regression analysis showed that glycohemoglobin was a negative predictor of the natural log(ln) peak serum V (R(2) = 0.40, p = 0.009) and a positive predictor of the euglycemic-hyperinsulinemic clamp results at high insulin values (R(2) = 0.39, p = 0.010). Insulin sensitivity measured by euglycemic-hyperinsulinemic clamp was not significantly correlated with ln peak serum V. Globulin and glycohemoglobin levels taken together were negative predictors of fasting blood glucose (R(2) = 0.49, p = 0.013). Although V accumulation in serum was dose-dependent, no correlation between total serum V concentration and the insulin-like response was found in this first attempt to correlate anti-diabetic activity with total serum V. This study suggests that V pools other than total serum V are likely related to the insulin-like effect of this metal. These results, obtained in diabetic patients, document the need for consideration of the coordination chemistry of metabolites and proteins with vanadium in anti-diabetic vanadium complexes.
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effect of vanadium iv compounds in the treatment of diabetes in vivo and in vitro studies with Vanadyl Sulfate and bis maltolato oxovandium iv
Journal of Inorganic Biochemistry, 2001Co-Authors: Gail R Willsky, J H Mcneill, Allison B Goldfine, Paul J Kostyniak, Luqin Yang, H R Khan, Debbie C CransAbstract:Vanadyl Sulfate (VOSO4) was given orally to 16 subjects with type 2 diabetes mellitus for 6 weeks at a dose of 25, 50, or 100 mg vanadium (V) daily [Goldfine et al., Metabolism 49 (2000) 1–12]. Elemental V was determined by graphite furnace atomic absorption spectrometry (GFAAS). There was no correlation of V in serum with clinical response, determined by reduction of mean fasting blood glucose or increased insulin sensitivity during euglycemic clamp. To investigate the effect of administering a coordinated V, plasma glucose levels were determined in streptozotocin (STZ)-induced diabetic rats treated with the salt (VOSO4) or the coordinated V compound bis(maltolato)oxovandium(IV) (abbreviated as VO(malto)2) administered by intraperitoneal (i.p.) injection. There was no relationship of blood V concentration with plasma glucose levels in the animals treated with VOSO4, similar to our human diabetic patients. However, with VO(malto)2 treatment, animals with low plasma glucose tended to have high blood V. To determine if V binding to serum proteins could diminish biologically active serum V, binding of both VOSO4 and VO(malto)2 to human serum albumin (HSA), human apoTransferrin (apoHTf) and pig immunoglobulin (IgG) was studied with EPR spectroscopy. Both VOSO4 and VO(malto)2 bound to HSA and apoHTf forming different V-protein complexes, while neither V compound bound to the IgG. VOSO4 and VO(malto)2 showed differences when levels of plasma glucose and blood V in diabetic rodents were compared, and in the formation of V-protein complexes with abundant serum proteins. These data suggest that binding of V compounds to ligands in blood, such as proteins, may affect the available pool of V for biological effects.
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metabolic effects of Vanadyl Sulfate in humans with non insulin dependent diabetes mellitus in vivo and in vitro studies
Metabolism-clinical and Experimental, 2000Co-Authors: Allison B Goldfine, Maryelizabeth Patti, Lubna Zuberi, Barry J GoldsteinAbstract:To investigate the efficacy and mechanism of action of vanadium salts as oral hypoglycemic agents, 16 type 2 diabetic patients were studied before and after 6 weeks of Vanadyl Sulfate (VOSO 4 ) treatment at three doses. Glucose metabolism during a euglycemic insulin clamp did not increase at 75 mg/d, but improved in 3 of 5 subjects receiving 150 mg VOSO 4 and 4 of 8 subjects receiving 300 mg VOS0 4 . Basal hepatic glucose production (HGP) and suppression of HGP by insulin were unchanged at all doses. Fasting glucose and hemoglobin A 1c (HbA 1c ) decreased significantly in the 150- and 300-mg VOSO 4 groups. At the highest dose, total cholesterol decreased, associated with a decrease in high-density lipoprotein (HDL). There was no change in systolic, diastolic, or mean arterial blood pressure on 24-hour ambulatory monitors at any dose. There was no apparent correlation between the clinical response and peak serum level of vanadium. The 150-and 300-mg Vanadyl doses caused some gastrointestinal intolerance but did not increase tissue oxidative stress as assessed by thiobarbituric acid-reactive substances (TBARS). In muscle obtained during clamp studies prior to vanadium therapy, insulin stimulated the tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1 (IRS-1 ), and She proteins by 2- to 3-fold, while phosphatidylinositol 3-kinase (PI 3-kinase) activity associated with IRS-1 increased 4.7-fold during insulin stimulation ( P = .02). Following vanadium, there was a consistent trend for increased basal levels of insulin receptor. She, and IRS-1 protein tyrosine phosphorylation and IRS-1—associated PI 3-kinase, but no further increase with insulin. There was no discernible correlation between tyrosine phosphorylation patterns and glucose disposal responses to Vanadyl. While glycogen synthase fractional activity increased 1.5-fold following insulin infusion, there was no change in basal or insulin-stimulated activity after Vanadyl. There was no increase in the protein phosphatase activity of muscle homogenates to exogenous substrate after Vanadyl. Vanadyl Sulfate appears safe at these doses for 6 weeks, but at the tolerated doses, it does not dramatically improve insulin sensitivity or glycemic control. Vanadyl modifies proteins in human skeletal muscle involved in early insulin signaling, including basal insulin receptor and substrate tyrosine phosphorylation and activation of PI 3-kinase, and is not additive or synergistic with insulin at these steps. Vanadyl Sulfate does not modify the action of insulin to stimulate glycogen synthesis. Since glucose utilization is improved in some patients, Vanadyl must also act at other steps of insulin action.
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metabolic effects of Vanadyl Sulfate in humans with n o n i n s u l i n d e p e n d e n t diabetes mellitus in vivo and in vitro studies
2000Co-Authors: Allison B Goldfine, Maryelizabeth Patti, Lubna Zuberi, Barry J Goldstein, Raeann Leblanc, Edwin J Landaker, Zhen Y Jiang, Gail R Willsky, Ronald C KahnAbstract:To investigate the efficacy and mechanism of action of vanadium salts as oral hypoglycemic agents, 16 type 2 diabetic patienl:s were studied before and after 6 weeks of Vanadyl Sulfate (VOSO4) treatment at three doses. Glucose metabolism during a euglycemic insulin clamp did not increase at 75 rag/d, but improved in 3 of 5 subjects receiving 150 mg VOSO4 and 4 of 8 subjects receiving 300 mg VOSO4. Basal hepatic glucose production (HGP) and suppression of HGP by insulin were unchanged at all doses. Fasting glucose and hemoglobin Ale (HbAlc) decreased significantly in the 150- and 300-rag VOSO4 groups. At the highest dose, total cholesterol decreased, associated with a decrease in high-density lipoprotein (HDL). There was no change in systolic, diastolic, or mean arterial blood pressure on 24-hour ambulatory monitors at any dose. There was no apparent correlation between the clinical response and peak serum level of vanadium. The 150- and 300-mg Vanadyl doses caused some gastrointestinal intolerance but did not increase tissue oxidative stress as assessed by thiobarbituric acid-reactive substances (TBARS). In muscle obtained during clamp studies prior to vanadium therapy, insulin stimulated the tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1 (IRS-1), and Shc proteins by 2- to 3-fold, while phosphatidyiinositol 3-kinase (PI 3-kinase) activity associated with IRS-1 increased 4.7-fold during insulin stimulation (P = .02). Following vanadium, there was a consistent trend for increased basal levels of insulin receptor, Shc, and IRS-1 protein tyrosine phosphorylation and IRS-l-associated PI 3-kinase, but no further increase with insulin. There was no discernible correlation between tyrosine phosphorylation patterns and glucose disposal responses to Vanadyl. While glycogen synthase fractional activity increased 1.5-fold following insulin infusion, there was no change in basal or insulin-stimulated activity after Vanadyl. There was no increase in the protein phosphatase activity of muscle homogenates to exogenous substrate after Vanadyl. Vanadyl Sulfate appears safe at these doses for 6 weeks, but at the tolerated doses, it does not dramatically improve insulin sensitivity or glycemic control. Vanadyl modifies proteins in human skeletal muscle involved in early insulin signaling, including basal insulin receptor and substrate tyrosine phosphorylation and activation of PI 3-kinase, and is not additive or synergistic with insulin at these steps. Vanadyl Sulfate does not modify the action of insulin to stimulate glycogen synthesis. Since glucose utilization is improved in some patients, Vanadyl must also act at other steps of insulin action. Copyright© 2000 by W.B. Saunders Company
