@article {https://doi.org/10.1002/elps.8139,
	title = {Characterization of Taurocholic Acid Binding With Insulin for Potential Oral Formulation Using Different Methods},
	journal = {ELECTROPHORESIS},
	volume = {in press},
	number = {n/a},
	year = {2025},
	abstract = {<p>ABSTRACT In diabetes management, oral formulation of insulin (INS) has the potential to improve safety, convenience, and patient-centered care compared to subcutaneous injections. However, its bioavailability remains limited, necessitating improved delivery strategies. Recent clinical trials indicate that taurocholic acid (TCA) can enhance the bioavailability of oral INS as an absorption enhancer. In this work, electrospray ionization mass spectrometry (ESI-MS) analysis revealed the formation of 1:1\&ndash;1:4 INS\&ndash;TCA complexes. MS/MS was used to explore the fragmentation pathway of complex ions and confirm binding stability in the gas phase. Circular dichroism spectra showed no clear conformational change in INS upon TCA binding, even though TCA enhanced INS\&$\#$39;s structural stability. Using Taylor dispersion analysis (TDA), we determined the diffusion coefficient and hydrodynamic radius of INS and its complexes. TCA binding was observed to increase INS size in both the 1:1 and 1:2 INS\&ndash;TCA complexes. The binding constant of INS and TCA (1.3 \&times; 103 L/mol) with approximately five binding sites was obtained via pressure-assisted capillary electrophoresis frontal analysis. Molecular docking simulations indicated that TCA binds to external binding sites on the INS B chain (near Ser-B9, Glu-B13, and Phe-B24 residues), consistent with ESI-MS and TDA results. These findings suggest that TCA binding may enhance INS absorption and increase the bioavailability of oral INS therapy.</p>},
	keywords = {capillary electrophoresis, INSULIN, interaction, MASS SPECTROMETRY, taurocholic acid},
	doi = {https://doi.org/10.1002/elps.8139},
	url = {https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/elps.8139},
	author = {Sun, Chang and Wang, Shuanghao and Li, Huihui and Chen, David D. Y.}
}
@article {1011,
	title = {Comparison of anti-hyperglycemic effect amongst vanadium, molybdenum and other metal maltol complexes},
	journal = {Journal of Inorganic Biochemistry},
	volume = {98},
	number = {5},
	year = {2004},
	note = {ISI Document Delivery No.: 824HVTimes Cited: 37Cited Reference Count: 7411th International Conference on Biological Inorganic ChemistryJUL 19-23, 2003Cairns, AUSTRALIA},
	month = {May},
	pages = {683-690},
	type = {Proceedings Paper},
	abstract = {A wide variety of vanadium-containing complexes have been tested, both in vivo and in vitro, as possible therapeutic agents for the oral treatment of type 2 diabetes mellitus. None so far has surpassed bis(maltolato)oxovanadium(IV) (BMOV) for glucose- and lipid-lowering in an orally available formulation. Ligand choice is clearly an important factor in pharmacological efficacy of vanadium compounds as insulin enhancing agents. In this study, we kept the ligand and dose the same, varying instead the metal ion bound to the maltolato ligand in a series of binary complexes of neutral charge. A requirement for vanadyl ion as the metal ion of choice was apparent; no other metal ion tested served as a suitable substitute. Amongst [MoO2](2+), Co(II), Cu(II), Cr(III), and Zn(II), only [MoO2](2+) and Co(II) showed any hypoglycemic activity at the ED50 dose for bis(maltolato)oxovanadium(IV), 0.6 mmol kg(-1) by oral gavage in streptozotocin (STZ)-diabetic rats within 72 It of administration of compound. (C) 2004 Elsevier Inc. All rights reserved.},
	keywords = {ABSORPTION, CHROMIUM, cobalt, COORDINATION MODE, copper, DEPENDENT DIABETES-MELLITUS, GLUCOSE-METABOLISM, IN-VIVO, INSULIN, LIPID-METABOLISM, MOLYBDENUM, RATS, VANADIUM, zinc, ZINC SUPPLEMENTATION},
	isbn = {0162-0134},
	url = {<Go to ISI>://000221678300004},
	author = {Thompson, K. H. and Chiles, J. and Yuen, V. G. and Tse, J. and McNeill, J. H. and Orvig, Chris}
}
@article {524,
	title = {Influence of chelation and oxidation state on vanadium bioavailability, and their effects on tissue concentrations of zinc, copper, and iron},
	journal = {Biological Trace Element Research},
	volume = {86},
	number = {1},
	year = {2002},
	note = {ISI Document Delivery No.: 541ZTTimes Cited: 27Cited Reference Count: 45},
	month = {Apr},
	pages = {31-44},
	type = {Article},
	abstract = {Today, vanadium compounds are frequently included in nutritional supplements and are also being developed for therapeutic use in diabetes mellitus. Previously, tissue uptake of vanadium from bis(maltolato)oxovanadium(IV) (BMOV) was shown to be increased compared to its uptake from vanadyl sulfate (VS). Our primary objective was to test the hypothesis that complexation increases vanadium uptake and that this effect is independent of oxidation state. A secondary objective was to compare the effects of vanadium complexation and oxidation state on tissue iron, copper, and zinc. Wistar rats were fed either ammonium metavanadate (AMV), VS, or BMOV (1.2 mM each in the drinking water). Tissue uptake of V following 12 wk of BMOV or AMV was higher than that from VS (p < 0.05). BMOV led to decreased tissue Zn and increased bone Fe content. The same three compounds were compared in a cellular model of absorption (Caco-2 cells). Vanadium uptake from VS was higher than that from BMOV or AMV at 10 min, but from BMOV (250 \&mu;M only, 60 min), uptake was far greater than from AMV or VS. These results show that neither complexation nor oxidation state alone are adequate predictors of relative absorption, tissue accumulation, or trace element interactions.},
	keywords = {ABSORPTION, BIS(MALTOLATO)OXOVANADIUM(IV), bone, CACO-2, Caco-2 cells, COMPLEXES, DIABETIC RATS, GLUCOSE-METABOLISM, IN-VITRO, INSULIN, kidney, ORTHO-VANADATE, skeletal muscle, SULFATE, VANADIUM, zinc},
	isbn = {0163-4984},
	url = {<Go to ISI>://000175018100004},
	author = {Thompson, K. H. and Tsukada, Y. and Xu, Z. M. and Battell, M. and McNeill, J. H. and Orvig, Chris}
}
@article {4399,
	title = {Kinetic analysis and comparison of uptake, distribution, and excretion of V-48-labeled compounds in rats},
	journal = {Journal of Applied Physiology},
	volume = {84},
	number = {2},
	year = {1998},
	note = {ISI Document Delivery No.: YU964Times Cited: 63Cited Reference Count: 43},
	month = {Feb},
	pages = {569-575},
	type = {Article},
	abstract = {Vanadium has been found to be orally active in lowering plasma glucose levels; thus it provides a potential treatment for diabetes mellitus. Bis(maltolato)oxovanadium(rv) (BMOV) is a well-characterized organovanadium compound that has been shown in preliminary studies to have a potentially useful absorption profile. Tissue distributions of BMOV compared with those of vanadyl sulfate (VS) were studied in Wistar rats by using V-48 as a tracer. In this study, the compounds were administered in carrier-added forms by either oral gavage or intraperitoneal injection. Data analyzed by a compartmental model, by using simulation, analysis, and modeling (i.e., SAAM II) software, showed a pattern of increased tissue uptake with use of V-48-BMOV compared with (VS)-V-48. The highest V-48 concentrations at 24 h after gavage were in bone, followed by kidney and liver. Most ingested V-48 was eliminated unabsorbed by fecal excretion. On average, V-48 concentrations in bone, kidney, and liver 24 h after oral administration of V-48-BMOV were two to three times higher than those of (VS)-V-48, which is consistent with the increased glucose-lowering potency of BMOV in acute glucose lowering compared with VS.},
	keywords = {ADIPOCYTES, analysis, and modeling, BIS(MALTOLATO)OXOVANADIUM(IV), compartmental modeling, diabetes, DISSOCIATION, FERRIC MALTOL, GLUCOSE, INDUCED DIABETIC RATS, INSULIN, insulin mimetic, METABOLISM, MOLYBDENUM, SIMULATION, SMALL-INTESTINE, Software, VANADIUM, VANADYL SULFATE},
	isbn = {8750-7587},
	url = {<Go to ISI>://000071774300025},
	author = {Setyawati, I. A. and Thompson, K. H. and Yuen, V. G. and Sun, Y. and Battell, M. and Lyster, D. M. and Vo, C. and Ruth, T. J. and Zeisler, S. and McNeill, J. H. and Orvig, Chris}
}
@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.}
}
@article {3521,
	title = {OXOBIS(2,4-PENTANEDIONATO)VANADIUM(IV), A REDETERMINATION},
	journal = {Acta Crystallographica Section C-Crystal Structure Communications},
	volume = {51},
	year = {1995},
	note = {ISI Document Delivery No.: QB320Times Cited: 11Cited Reference Count: 7Part 1},
	month = {Jan},
	pages = {12-14},
	type = {Article},
	abstract = {A redetermination of oxobis(2,4-pentanedionato)vanadium(IV), [VO(C5H7O2)2], has been undertaken using high-resolution Mo data. Geometrical parameters do not differ significantly from those reported earlier [Dodge, Templeton and Zalkin (1961). J. Chem. Phys. 35, 55-67; Hen, Belford \& Pfluger (1965). J. Chem. Phys. 43, 3111-3115], but the standard deviations are improved by an order of magnitude. Important structural parameters: V-O(basal) 1.967(1)-1.970(1)Angstrom and V=O(apical) 1.584(2)Angstrom.},
	keywords = {INSULIN},
	isbn = {0108-2701},
	url = {<Go to ISI>://A1995QB32000006},
	author = {Shuter, E. and Rettig, S. J. and Orvig, Chris}
}
@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.}
}
