@article {2637,
	title = {Vanadium treatment of type 2 diabetes: A view to the future},
	journal = {Journal of Inorganic Biochemistry},
	volume = {103},
	number = {4},
	year = {2009},
	note = {ISI Document Delivery No.: 429EUTimes Cited: 20Cited Reference Count: 41Thompson, Katherine H. Lichter, Jay LeBel, Carl Scaife, Michael C. McNeill, John H. Orvig, Chris6th International Vanadium SymposiumJUL 17-19, 2008Lisbon, PORTUGALSp. Iss. SI},
	month = {Apr},
	pages = {554-558},
	type = {Proceedings Paper},
	abstract = {3-Hydroxy-2-methyl-4-pryone and 2-ethyl 3-hydroxy-4-pyrone (maltol and ethyl maltol, respectively) have proven especially suitable a ligands for vanadyl tons, fit potential insulin enhancing agents for diabetes mellitus. Both bis(maltolato)oxovanadium(IV) (BMOV), and the ethylmaltol analog, bis(ethylmaltolato)oxovanadium(IV) (BEOV), have the desired intermediate stability for pro-drug use, and have undergone extensive pie-clinical testing for safety and efficacy. Pharmacokinetic evaluation indicates a pattern of biodistribution consistent with fairly rapid dissociation and uptake, binding to serum transferrin for systemic circulation and transport to tissues, with preferential uptake in bone. These bis-ligand oxovanadium(IV) (VOL2) compounds have a clear advantage over inorganic vanadyl sulfate in terms of bioavailability and pharmaceutical efficacy. BEOV has now completed Phase I and has advanced to Phase II clinical trials. In the Phase I trial, a ran-e of doses horn 10 mg, to 90 mg BEOV, given orally to non-diabetic volunteers, resulted in no adverse effects, all biochemical parameters remained within normal limits. In the Phase IIa trial, BEOV (AKP-020). 20 mg, daily for 28 clays, per os, in seven type 2 diabetic Subjects, was associated with reductions in fasting blood and glucose and \%HbA1c; improved responses to oral glucose tolerance testing, versus, the observed worsening of diabetic symptoms in the two placebo controls. (C) 2009 Elsevier Inc. All rights reserved.},
	keywords = {BIODISTRIBUTION, bis(ethylmaltolato)oxovanadium(IV), BIS(MALTOLATO)OXOVANADIUM(IV), CHEMISTRY, Diabetes mellitus, IN-VIVO, INSULIN SENSITIVITY, MALTOL, METAL-COMPLEXES, RATS, SERUM, SKELETAL-MUSCLE, SULFATE, VANADIUM},
	isbn = {0162-0134},
	url = {<Go to ISI>://000264904400011},
	author = {Thompson, K. H. and Lichter, J. and Lebel, C. and Scaife, M. C. and McNeill, J. H. and Orvig, Chris}
}
@article {1103,
	title = {Dissecting the domain structure of Cdc4p, a myosin essential light chain involved in Schizosaccharomyces pombe cytokinesis},
	journal = {Biochemistry},
	volume = {44},
	number = {36},
	year = {2005},
	note = {ISI Document Delivery No.: 962ZGTimes Cited: 3Cited Reference Count: 75},
	month = {Sep},
	pages = {12136-12148},
	type = {Article},
	abstract = {Cytokinesis is the process by which one cell divides into two. Key in the cytokinetic mechanism of Schizosaccharomyces pombe is the contractile ring myosin, which consists of two heavy chains (Myo2p), two essential light chains (Cdc4p), and two regulatory light chains (R1c1p). Cdc4p is a dumbbell-shaped EF-hand protein composed of N- and C-terminal domains separated by a flexible linker. The properties of these two domains are of particular interest because each is hypothesized to have independent functions in binding different components of the cytokinesis machinery. To help define these properties, we used NMR spectroscopy to compare the structure, stability, and dynamics of the isolated N- and C-terminal domains with one another and with native Cdc4p. On the basis of invariant chemical shifts, the N-domain retains the same structure in isolation as in the context of the full-length Cdc4p, whereas the C-domain appears markedly perturbed. This perturbation results from intramolecular binding of the residual linker sequence at the N-terminus of the C-domain in a mode similar to that used by native Cdc4p to associate with target polypeptide sequences. NMR relaxation, thermal denaturation, and amide hydrogen exchange experiments also indicate that the C-domain is less stable and more dynamic than the N-domain, both in isolation and in the full-length protein. We hypothesize that these properties reflect a conformational plasticity of the C-domain, which may allow Cdc4p to interact with several regulatory or contractile ring proteins necessary for cytokinesis.},
	keywords = {CALCIUM-MODULATED PROTEINS, CONFORMATIONAL CHANGE, CONTRACTILE RING, FISSION, GROUP, HYDROGEN-EXCHANGE, MUSCLE TROPONIN-C, N-15 NMR RELAXATION, NUCLEAR MAGNETIC-RESONANCE, SACCHAROMYCES-CEREVISIAE, SKELETAL-MUSCLE, YEAST},
	isbn = {0006-2960},
	url = {<Go to ISI>://000231771500022},
	author = {Escobar-Cabrera, E. and Venkatesan, M. and Desautels, M. and Hemmingsen, S. M. and McIntosh, L. P.}
}
@article {784,
	title = {Chronic glucose-lowering effects of rosiglitazone and bis(ethylmaltolato)oxovanadium(IV) in ZDF rats},
	journal = {Canadian Journal of Physiology and Pharmacology},
	volume = {81},
	number = {11},
	year = {2003},
	note = {ISI Document Delivery No.: 749AHTimes Cited: 3Cited Reference Count: 47},
	month = {Nov},
	pages = {1049-1055},
	type = {Article},
	abstract = {The aim of this study was to determine if there was a synergistic or additive effect of a thiazolidinedione derivative (rosiglitazone (ROS)) and a vanadium compound (bis(ethylmaltolato)oxovanadium(IV) (BEOV)) on plasma glucose and insulin levels following chronic oral administration to Zucker diabetic fatty (ZDF) rats. Whole-blood vanadium levels were determined at time 0 and at days 1, 6, and 18. The doses of BEOV (0.1 mmol/kg) and ROS (2.8 mumol/kg) were selected to produce a glucose-lowering effect in 30\% (ED30) of animals. Both drugs were administered daily by oral gavage as suspensions in 1\% carboxymethylcellulose (CMC) in a volume of 2.5 mL/kg. The total volume administered to all rats was 5 mL/(kg-day). The combination of BEOV and ROS was effective in lowering plasma glucose levels to <9 mmol/L in 60\% of fatty animals as compared with 30\% for BEOV and 10\% for ROS alone. The age-dependent decrease in plasma insulin levels associated with \&beta;-cell failure in the ZDF rats did not occur in the BEOV-treated fatty groups. There was no effect of any treatment on body weight; however, there was a significant reduction in both food and fluid intake in fatty groups treated with BEOV. There were no overt signs of toxicity and no mortality in this study. Both BEOV and ROS were effective in lowering plasma glucose levels, as stated above, and there was at least an additive effect when BEOV and ROS were used in combination.},
	keywords = {ACTIVATED-RECEPTOR-GAMMA, bis(ethylmaltolato)oxovanadium(IV), diabetes, GLUT4, IN-VIVO, INSULIN SENSITIVITY, ORAL VANADYL, PHOSPHOENOLPYRUVATE-CARBOXYKINASE, RATS, rosigitazone, SKELETAL-MUSCLE, STREPTOZOTOCIN-DIABETIC RATS, TRANSLOCATION, VANADYL SULFATE, ZDF rats, ZUCKER FATTY},
	isbn = {0008-4212},
	url = {<Go to ISI>://000186896100007},
	author = {Yuen, V. G. and Bhanot, S. and Battell, M. L. and Orvig, Chris and McNeill, J. H.}
}
@article {4957,
	title = {Design of vanadium compounds as insulin enhancing agents},
	journal = {Journal of the Chemical Society-Dalton Transactions},
	number = {17},
	year = {2000},
	note = {ISI Document Delivery No.: 348MDTimes Cited: 77Cited Reference Count: 123},
	pages = {2885-2892},
	type = {Review},
	abstract = {Vanadium compounds, in vitro, stimulate glucose uptake and inhibit lipid breakdown, in a manner remarkably reminiscent of insulin{\textquoteright}s effects. In vivo, vanadium enhances insulin{\textquoteright}s plasma glucose and lipid-lowering properties, leading to normalization of diabetic symptoms in the presence of only minimal endogenous insulin. The coordination chemistry of vanadium has great versatility for adjustment of pharmacological characteristics. Vanadium compounds are generally also very redox active, which is both advantageous and detrimental for optimizing biochemical function. In this perspective, we review and comment on how these properties have been revealed, what questions have arisen along the way, and where future investigations may be headed. While this is not a comprehensive overview of all available compounds touted as {\textquoteright}insulin enhancing agents{\textquoteright}, it will focus on those which are distinctive in some way, or which are representative of the larger library of vanadium compounds, including all currently known relevant oxidation states of vanadium.},
	keywords = {AGENT, BIOLOGICAL-SYSTEMS, DEPENDENT DIABETES-MELLITUS, ECHO ENVELOPE, GLUCOSE-METABOLISM, IN-VIVO, MIMETIC, MODULATION, PEROXOVANADIUM COMPOUNDS, SKELETAL-MUSCLE, STREPTOZOTOCIN-TREATED RATS, TYROSINE PHOSPHORYLATION},
	isbn = {1470-479X},
	url = {<Go to ISI>://000088987800001},
	author = {Thompson, K. H. and Orvig, Chris}
}
@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.}
}
