@article {951,
	title = {Synthesis and insulinomimetic activities of novel mono- and tetranuclear oxovanadium(IV) complexes with 3-hydroxypyridine-2-carboxylic acid},
	journal = {Journal of Inorganic Biochemistry},
	volume = {98},
	number = {1},
	year = {2004},
	note = {ISI Document Delivery No.: 760DETimes Cited: 24Cited Reference Count: 21},
	month = {Jan},
	pages = {105-112},
	type = {Article},
	abstract = {Two chargeless VO(IV) complexes with 3-hydroxypyridine-2-carboxylic acid (H(2)hpic), [VO(Hhpic-O,O)(Hhpic-O,N)(H2O)(.)3H(2)O (1) and the cyclic tetramer [(VO)4(mu-(hpic-O,O,N))(4)(H2O)(4)](.)8H(2)O (2), have been synthesized and characterized by elemental analysis, mass, infrared, electronic absorption, electron spin resonance (ESR) spectroscopies, and X-ray crystallography. Their coordination structures are similar to each other (and 1 is readily transformed into 2), but are quite different from that of bis(pyridine-2-carboxylato)oxovanadium(IV). The magnetic susceptibility of 2 indicates the presence of a weak ferromagnetic intramolecular interaction between the V atoms at low temperature, in addition to a weak antiferromagnetic intermolecular interaction. The ESR signal of 2 was broad, while I showed an eight-line hyperfine splitting pattern due to coupling of the impaired electron with the V-51 nucleus (I = 7/2). The ESR spectrum and cyclic voltammogram of 2 clearly show that the cyclic tetramer remains intact in solution. The insulinomimetic activity of 1 and 2 was evaluated by means of in vitro measurements of the inhibition of free fatty acid release from epinephrine-treated isolated rat adipocytes. While I exerted higher insulinomimetic activity than VOSO4, the activity of 2 was significantly lower than that of VOSO4. Hence 2 appears to retain its cyclic structure during the in vitro test. These results indicate that the rational ligand design for VO complexes might be a promising approach to obtain superior insulinomimetic activity. (C) 2003 Elsevier Inc. All rights reserved.},
	keywords = {BLOOD-GLUCOSE, cyclic tetranuclear complex, INDUCED DIABETIC RATS, insulinomimetic activity, oxovanadium, SOLID-STATE, VANADIUM(IV), VANADYL COMPLEX},
	isbn = {0162-0134},
	url = {<Go to ISI>://000187795700014},
	author = {Nakai, M. and Obata, M. and Sekiguchi, F. and Kato, M. and Shiro, M. and Ichimura, A. and Kinoshita, I. and Mikuriya, M. and Inohara, T. and Kawabe, K. and Sakurai, H. and Orvig, Chris and Yano, S.}
}
@article {742,
	title = {Vanadyl-thiazolidinedione combination agents for diabetes therapy},
	journal = {Bioconjugate Chemistry},
	volume = {14},
	number = {1},
	year = {2003},
	note = {ISI Document Delivery No.: 637YYTimes Cited: 23Cited Reference Count: 42},
	month = {Jan-Feb},
	pages = {212-221},
	type = {Article},
	abstract = {A series of vanadium compounds, chelated by ligands containing a thiazolidinedione moiety as an additional insulin-enhancing component, were produced in this study to create potentially synergistic compounds. A set of four bifunctional ligand precursors were synthesized: (+/-)-5-4-[(5-hydroxy-4-oxo-4H-pyran-2-ylmethyl)amino]benzylthiazolidi ne-2,4-dione (HL1), (+/-)-5-4-[5-hydroxy-1-methyl-4-oxo-1,4-dihydro-pyridin-2-ylmethyl)amin o]benzylthiazolidine-2,4-dione (HL2) 5-[4-(5-hydroxy-4-oxo-4H-pyran-2-ylmethoxy)benzylidenelthiazolidine-2,4- dione (HL1), and (+/-)-5-4-(5-hydroxy-4-oxo-4H-pyran-2-ylmethoxy)benzyl]thiazolidine-2,4 -dione (HL4), each containing a metal chelating portion as well as a thiazolidinedione moiety. From this set of ligand precursors, air-stable VO(L-1)(2), VO(L-3)(2), and VO(L-4)(2) were prepared. The four ligand precursors and three complexes were tested for insulin-enhancing potential in STZ-diabetic rats and compared to rosiglitazone and BMOV, respectively. Both the ligand precursors HL1 and HL3 showed enhanced activity compared with that of rosiglitazone. The complex VO(L-3)(2) showed the most efficacious hypoglycemic effects in this study; however, neither additive nor synergistic effects were observed using this acute animal model.},
	keywords = {AGENT, ANTIHYPERGLYCEMIC, BIOLOGICAL-ACTIVITY, BIS(MALTOLATO)OXOVANADIUM(IV), BLOOD-GLUCOSE, COMPLEXES, DERIVATIVES, GLUCOSE-LOWERING PROPERTIES, INSULIN MIMETIC AGENT, RAT ADIPOCYTES, TROGLITAZONE},
	isbn = {1043-1802},
	url = {<Go to ISI>://000180542400025},
	author = {Storr, T. and Mitchell, D. and Buglyo, P. and Thompson, K. H. and Yuen, V. G. and McNeill, J. H. and Orvig, Chris}
}
@article {499,
	title = {Effects of diabetes, vanadium, and insulin on glycogen synthase activation in Wistar rats},
	journal = {Molecular and Cellular Biochemistry},
	volume = {231},
	number = {1-2},
	year = {2002},
	note = {ISI Document Delivery No.: 527LATimes Cited: 21Cited Reference Count: 51},
	month = {Feb},
	pages = {23-35},
	type = {Article},
	abstract = {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.},
	keywords = {BLOOD-GLUCOSE, GLUCOSE-TRANSPORT, glycogen, IN-VITRO, insulin resistance, MELLITUS, MOLECULAR MECHANISM, PHOSPHORYLATION, PROTEIN-KINASE-B, RABBIT SKELETAL-MUSCLE, S6 KINASE, serine/threonine kinases and phosphatases, streptozotocin-induced diabetes, SYNTHESIS, VANADATE},
	isbn = {0300-8177},
	url = {<Go to ISI>://000174186500004},
	author = {Semiz, S. and Orvig, Chris and McNeill, J. H.}
}
@article {3578,
	title = {COMPARISON OF THE GLUCOSE-LOWERING PROPERTIES OF VANADYL SULFATE AND BIS(MALTOLATO)OXOVANADIUM(IV) FOLLOWING ACUTE AND CHRONIC ADMINISTRATION},
	journal = {Canadian Journal of Physiology and Pharmacology},
	volume = {73},
	number = {1},
	year = {1995},
	note = {ISI Document Delivery No.: QN264Times Cited: 71Cited Reference Count: 31},
	month = {Jan},
	pages = {55-64},
	type = {Article},
	abstract = {Numerous studies, bath in vitro and in vivo, have demonstrated the insulin-mimetic properties of vanadium. Chronic oral administration of inorganic and organic compounds of both vanadium(IV) and vanadium(V) reduced plasma glucose levels and restored plasma lipid levels in streptozotocin-diabetic rats. We investigated the acute effects of both vanadyl sulfate and bis(maltolato)oxovanadium(IV) (BMOV), an organic vanadium compound, on plasma glucose levels by several routes of administration. Previous studies have shown that chronic administration of vanadyl sulfate has resulted in a sustained euglycemia following withdrawal of the drug. This effect was not observed following the chronic administration of BMOV; therefore, we investigated the effect of increasing the concentration of BMOV on the production of a sustained euglycemic response. An acute plasma glucose lowering effect was obtained with both vanadyl sulfate and BMOV when administered as a single dose by either oral gavage or intraperitoneal injection. In those animals that responded to vanadium treatment, plasma glucose levels were within the normal range within 2 to 6 h when given by i.p. injection or within 4 to 8 h when given by oral gavage. BMOV-treated rats that responded to treatment maintained the euglycemic effect for extended periods, ranging from 1 to 14 weeks following administration. However, vanadyl sulfate treated rats reverted to hyperglycemia within 12 to 24 h, depending on the route of administration. Intravenous administration of BMOV was effective in lowering plasma glucose levels only when administered by continuous infusion. An oral dose - response curve showed that BMOV was 2 to 3 times as potent as vanadyl sulfate. This difference in potency was observed with both oral and intraperitoneal administration, which suggests that the increase in potency with BMOV cannot be totally attributed to increased gastrointestinal absorption. Organic chelation of vanadium may facilitate uptake into vanadium-sensitive tissues. Chronic oral administration of higher concentrations of BMOV did not result in a sustained reduction in plasma glucose following withdrawal of the drug. All diabetic rats eventually responded to increased concentrations of BMOV with a restoration of plasma glucose levels to normal values; however, reversion to the hyperglycemic state occurred within 2 days of withdrawal of treatment. Chronic oral administration of BMOV did not produce a sustained euglycemic effect following withdrawal, but acute administrations of the compound by either oral gavage or intraperitoneal injection did produce a long-term reduction in plasma glucose levels. Rats treated chronically with vanadyl sulfate remained euglycemic even after the drug was withdrawn. However, acute treatment produced only a transient euglycemia.},
	keywords = {ACUTE, BIS(MALTOLATO)OXOVANADIUM(IV), BLOOD-GLUCOSE, DOSE RESPONSE, GAVAGE, HOMEOSTASIS, IMPROVEMENT, INDUCED DIABETIC RATS, INSULIN, STREPTOZOTOCIN DIABETIC, SULFATE, VANADYL},
	isbn = {0008-4212},
	url = {<Go to ISI>://A1995QN26400008},
	author = {Yuen, V. G. and Orvig, Chris and McNeill, J. H.}
}
@inbook {3468,
	title = {VANADIUM COMPOUNDS AS INSULIN MIMICS},
	booktitle = {Metal Ions in Biological Systems, Vol 31},
	series = {Metal Ions in Biological Systems},
	volume = {31},
	year = {1995},
	note = {ISI Document Delivery No.: BD60ZTimes Cited: 106Cited Reference Count: 126Review270 MADISON AVE, NEW YORK, NY 10016},
	pages = {575-594},
	publisher = {Marcel Dekker},
	organization = {Marcel Dekker},
	address = {New York},
	keywords = {AMINO-ACID, ANTIOXIDANT STATUS, BLOOD-GLUCOSE, GLYCOGEN-SYNTHASE, INSULINOMIMETIC AGENTS, LEVELS, ORAL VANADYL, RECEPTOR TYROSINE KINASE, SKELETAL-MUSCLE, STREPTOZOTOCIN-DIABETIC RATS, VANADATE TREATMENT},
	isbn = {0161-5149},
	url = {<Go to ISI>://A1995BD60Z00017},
	author = {Orvig, Chris and Thompson, K. H. and Battell, M. and McNeill, J. H.}
}
@article {2940,
	title = {GLUCOSE-LOWERING EFFECTS OF A NEW ORGANIC VANADIUM COMPLEX, BIS(MALTOLATO)OXOVANADIUM(IV)},
	journal = {Canadian Journal of Physiology and Pharmacology},
	volume = {71},
	number = {3-4},
	year = {1993},
	note = {ISI Document Delivery No.: LN775Times Cited: 84Cited Reference Count: 39},
	month = {Mar-Apr},
	pages = {263-269},
	type = {Article},
	abstract = {Inorganic vanadium has been shown, both in vivo and in vitro, to have insulin-mimetic properties. A new organic vanadium complex, bis(maltolato)oxovanadium(IV) (BMOV), was developed to increase the absorption of vanadium from the gastrointestinal tract, thereby reducing the dose of vanadium necessary to produce glucose-lowering effects. BMOV was administered in the drinking water for 25 weeks to control and streptozotocin-induced diabetic, male Wistar rats. BMOV treatment produced a stable euglycemic state in 70\% of diabetic treated animals. The other 30\% of the diabetic treated animals demonstrated fluctuations in glucose control over the entire study period. The initial effective dose of BMOV was 0.45 mmol/kg, which decreased to an effective maintenance dose of 0. 18 mmol/kg, significantly lower than the dose of inorganic vanadium salts used in previous studies. BMOV treatment did significantly reduce fluid consumption levels in control treated animals after 10 weeks of therapy; however, the food consumption for control treated animals was only intermittently lower than that for controls. Plasma cholesterol and triglyceride levels were normalized with BMOV treatment for all diabetic treated animals, without a concomitant increase in plasma insulin levels. An oral glucose tolerance test demonstrated that glucose homeostasis in control-treated animals occurred at significantly lower plasma insulin levels than in control animals. BMOV effectively produced the glucose-lowering effects at significantly lower dose than previously used for inorganic vanadium salts, without any overt signs of toxicity.},
	keywords = {ACTIVATION, ADIPOCYTES, BIS(MALTOLATO)OXOVANADIUM(IV), BLOOD-GLUCOSE, DIABETES TREATMENT, DIABETIC RATS, GLYCOLYSIS, INSULIN, SENSITIVITY, SKELETAL-MUSCLE, STIMULATION, streptozotocin-induced diabetes, VANADATE},
	isbn = {0008-4212},
	url = {<Go to ISI>://A1993LN77500013},
	author = {Yuen, V. G. and Orvig, Chris and McNeill, J. H.}
}
@article {2941,
	title = {IMPROVEMENT IN CARDIAC DYSFUNCTION IN STREPTOZOTOCIN-INDUCED DIABETIC RATS FOLLOWING CHRONIC ORAL-ADMINISTRATION OF BIS(MALTOLATO)OXOVANADIUM(IV)},
	journal = {Canadian Journal of Physiology and Pharmacology},
	volume = {71},
	number = {3-4},
	year = {1993},
	note = {ISI Document Delivery No.: LN775Times Cited: 70Cited Reference Count: 40},
	month = {Mar-Apr},
	pages = {270-276},
	type = {Article},
	abstract = {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 mug/mL (16.8 muM) in CT rats and 0.76 +/-0.05 mug/mL (15.2 muM) in DT animals. The highest vanadium levels at termination of this chronic feeding study were in bone, 18.3 +/- 3.0 mug/g (0.37 mumol/g) in CT and 26.4 +/- 2.6 mug/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 die glucose-lowering effect. Isolated working heart parameters of left ventricular developed pressure (LVDP) and rate of pressure development (+dP/dT, and -dP/dT) indicated that BMOV treatment resulted in significant correction of the heart dysfunction associated with streptozotocin-induced diabetes in rat.},
	keywords = {ACTIVATION, BIS(MALTOLATO)OXOVANADIUM(IV), BLOOD-GLUCOSE, diabetes, GLUCOSE-HOMEOSTASIS, INSULIN, MYOCARDIAL DYSFUNCTION, STREPTOZOTOCIN, SULFATE, VANADATE TREATMENT, VANADIUM},
	isbn = {0008-4212},
	url = {<Go to ISI>://A1993LN77500014},
	author = {Yuen, V. G. and Orvig, Chris and Thompson, K. H. and McNeill, J. H.}
}
