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Comparison of intestinal absorption of two insulin-mimic vanadyl complexes using Caco-2 monolayers as model system

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Chinese Science Bulletin

Abstract

Intestinal absorption of two oxovanadium complexes, vanadyl acetylacetonate (VO(acac)2) and bis-(maltolato)-oxovanadium (VO(ma)2), has been compared using Caco-2 monolayers as a model system. The two compounds are similar in chemical structures but different in glucose-lowering effects. Our experimental results show that they are both transported via passive diffusion with apparent permeabilty coefficients (apical → basolateral) of (82.0 ± 6.7)×10−7 and (14.6 ± 0.7) ×10−7 cm · s−1 respectively. This suggests that absorptivity of VO(acac)2 is much higher than that of VO(ma)2. This difference may be related to the metabolism of either compound, or its ligand, or both in the course of the transport. However, This difference in absorption will cause the great difference in bioavailability, which might account for better efficacy of VO(acac)2 than VO(ma)2 as the insulin-mimic agent.

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References

  1. Shechter, Y, Shisheva, A., Vanadium salt and the future treatment of diabetes, Endeavour, 1993, 17(1): 27–31.

    Article  Google Scholar 

  2. Shechter, Y, Karlish, S. J., Insulin-like stimulation of glucose oxidation in rat adipocytes by vanadyl (IV) ions, Nature, 1980, 284(5756): 556–558.

    Article  Google Scholar 

  3. Posner, B. I, Faure, R, Burgess, J. W. et al., Peroxovanadium compounds, A new class of potent phosphotyrosine phosphatase inhibitors which are insulin mimetics, J. Biol. Chem., 1994, 269(6): 4596–4604.

    Google Scholar 

  4. Fantus, I. G, Tsiani, E., Multifunctional actions of vanadium compounds on insulin signaling pathways: Evidence for preferential enhancement of metabolic versus mitogenic effects, Mol. Cell Biochem., 1998, 182(1–2): 109–119.

    Article  Google Scholar 

  5. Thompson, K. H, McNeill, J. H, Orvig, C., Vanadium compounds as insulin mimics, Chem. Rev., 1999, 99(9): 2561–2572.

    Article  Google Scholar 

  6. Yuen, V. G, Orvig, C, McNeill, J. H., Glucose-lowering effects of a new organic vanadium complex, bis(maltolato)oxovanadium (IV), Can. J. Physiol. Pharmacol., 1993, 71(3–4): 263–269.

    Article  Google Scholar 

  7. Yuen, V. G, Orvig, C, McNeill, J. H., Comparison of the glucose-lowering properties of vanadyl sulfate and bis(maltolato) oxovanadium(IV) following acute and chronic administration, Can. J. Physiol. Pharmacol., 1995, 73(1): 55–64.

    Article  Google Scholar 

  8. Reul, B. A, Amin, S. S, Buchet, J. P. et al., Effects of vanadium complexes with organic ligands on glucose metabolism: A comparison study in diabetic rats, Br. J. Pharmacol., 1999, 126(2): 467–477.

    Article  Google Scholar 

  9. Yang, X. G., Lu, J. F., Wang, K., Across membrane transport, transformation and cytotoxicity of anti-diabetes vanadium compounds: An in vitro study with human erythrocytes as model system, Third International Symposium on Chemistry and Biological Chemistry of Vanadium, Osaka, 2001.

    Google Scholar 

  10. Sekar, N, Li, J, Shechter, Y., Vanadium salts as insulin substitutes: Mechanisms of action, a scientific and therapeutic tool in diabetes mellitus research, Crit. Rev. Biochem. Mol. Biol., 1996, 31(5–6): 339–359.

    Article  Google Scholar 

  11. Miralpeix, M, Decaux, J. F, Kahn, A. et al., Vanadate induction of L-type pyruvate kinase mRNA in adult rat hepatocytes in primary culture, Diabetes, 1991, 40(4): 462–464.

    Article  Google Scholar 

  12. Bosch, F, Hatzoglou, M, Park, E. A. et al., Vanadate inhibits expression of the gene for phosphoenolpyruvate carboxykinase (GTP) in rat hepatoma cells, J. Biol. Chem., 1990, 265(23): 13677–13682.

    Google Scholar 

  13. Borchardt, R. T, Pharmaceutical applications of cell culture: An overview, Pharmaceutical Applications of Cell and Tissue Culture to Drug Transport, New York: Plenum Press, 1991.

    Google Scholar 

  14. Walle, U. K, Walle, T., Taxol transport by human intestinal epithelial Caco-2 cells, Drug Metab Dispos, 1998, 26(4): 343–346.

    Google Scholar 

  15. Chasseaud, L. F., Accelerating ADME studies, Hum. Exp. Toxicol., 1995, 14(12): 991–992.

    Article  Google Scholar 

  16. Coleman, R. A, Bowen, W. P, Baines, I. A. et al., Use of human tissue in ADME and safety profiling of development candidates, Drug Discov. Today, 2001, 6(21): 1116–1126.

    Article  Google Scholar 

  17. Eddershaw, P. J, Beresford, A. P, Bayliss, M. K., ADME/PK as part of a rational approach to drug discovery, Drug Discov. Today, 2000, 5(9): 409–414.

    Article  Google Scholar 

  18. Ekins, S, Waller, C. L, Swaan, P. W. et al., Progress in predicting human ADME parameters in silico, J. Pharmacol. Toxicol. Methods, 2000, 44(1): 251–272.

    Article  Google Scholar 

  19. Ekins, S, Rose, J., In silico ADME/Tox: The state of the art, J. Mol. Graph. Model, 2002, 20(4): 305–309.

    Article  Google Scholar 

  20. Li, A. P., Screening for human ADME/Tox drug properties in drug discovery, Drug Discov. Today, 2001, 6(7): 357–366.

    Article  Google Scholar 

  21. Li, A. P, Segall, M., Early ADME/Tox studies and in silico screening, Drug Discov. Today, 2002, 7(1): 25–27.

    Article  Google Scholar 

  22. Selick, H. E, Beresford, A. P, Tarbit, M. H., The emerging importance of predictive ADME simulation in drug discovery, Drug Discov. Today, 2002, 7(2): 109–116.

    Article  Google Scholar 

  23. Yamashita, S, Furubayashi, T, Kataoka, M. et al., Optimized conditions for prediction of intestinal drug permeability using Caco-2 cells, Eur. J. Pharm. Sci., 2000, 10(3): 195–204.

    Article  Google Scholar 

  24. Hidalgo, I. J, Raub, T. J, Borchardt, R. T., Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability, Gastroenterology, 1989, 96(3): 736–749.

    Google Scholar 

  25. Artursson, P, Karlsson, J., Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells, Biochem. Biophys. Res. Commun., 1991, 175(3): 880–885.

    Article  Google Scholar 

  26. Artursson, P, Palm, K, Luthman, K., Caco-2 monolayers in experimental and theoretical predictions of drug transport, Adv. Drug. Deliv. Rev., 2001, 46(1–3): 27–43.

    Article  Google Scholar 

  27. Sun, Y, James, B. R, Rettig, S. J. et al., Oxidation Kinetics of the Potent Insulin Mimetic Agent Bis(maltolato)oxovanadium(IV) (BMOV) in Water and in Methanol, Inorg. Chem., 1996, 35(6): 1667–1673.

    Article  Google Scholar 

  28. Crans, D. C., Chemistry and insulin-like properties of vanadium(IV) and vanadium(V) compounds, J. Inorg. Biochem., 2000, 80(1–2): 123–131.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100083, China

    Xiaogai Yang, Kui Wang & Xiaoda Yang

  2. National Research Laboratories of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100083, China

    Kui Wang & Xiaoda Yang

  3. Laboratories of Preventive Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100083, China

    Kui Wang & Xiaoda Yang

  4. Analytical Center of Peking University, Beijing, 100083, China

    Lan Yuan

Authors
  1. Xiaogai Yang
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  2. Lan Yuan
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  3. Kui Wang
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  4. Xiaoda Yang
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Correspondence to Xiaoda Yang.

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Yang, X., Yuan, L., Wang, K. et al. Comparison of intestinal absorption of two insulin-mimic vanadyl complexes using Caco-2 monolayers as model system. Chin.Sci.Bull. 48, 876–881 (2003). https://doi.org/10.1007/BF03325668

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  • DOI: https://doi.org/10.1007/BF03325668

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