Biological Trace Element Research

, Volume 80, Issue 2, pp 159–174 | Cite as

Effect of long-term treatment with vanadate in drinking water on KK mice with genetic non-insulin-dependent diabetes mellitus

  • Wenjun Ding
  • Tatsuya Hasegawa
  • Hitomi Hosaka
  • Duan Peng
  • Koji Takahashi
  • Yoshiyuki Seko


The glucose-lowering effect of vanadate, ammonium metavanadate (AMV), on diabetic KK mice was examined. Five-week-old male KK mice were administrated with a solution of AMV via drinking water at concentrations of vanadium (V) with 0.1, 1.0, 10 and 100 µg/mL for a period of 10 wk, respectively. Body weight, consumption of food and water, and blood glucose levels was measured every week for 10 wk. The results showed that food consumption and body weight in the experimental groups were similar to those in the control group. A statistically significant decrease of drinking water consumption and blood glucose levels in the group treated with 100 µg V/mL was observed. The glucose tolerance in the vanadate-treated mice with 10 and 100 µg V/mL was remarkably improved compared with the control group. Biochemical analyses at the end of experiments demonstrated that a distinct tendency for the glucose and hemoglobin A1c (HbA1c) levels to decrease with vanadate treatment in the blood was also observed. The glutamic pyruvic transaminase, glutamic oxaloacetate transaminase, blood urea nitrogen, triglyceride, high-density lipoprotein, and total cholesterol levels in plasma were lower in the higher vanadium groups than those in the control group. These results indicate that vanadium effectively produced the glucose-lowering effect at a higher dose than that at a low dose of vanadium in drinking water, without any overt signs of toxicity.

Index Entries

Vanadate non-insulin-dependent diabetes mellitus KK mouse glucose-lowering effect 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    S. Dinneen, J. Gerich, and R. Rizza, Carbohydrate metabolism in non-insulin-dependent diabetes mellitus, N. Engl. J. Med. 327, 707–713 (1992).PubMedCrossRefGoogle Scholar
  2. 2.
    E. L. Tolman, E. Barris, M. Burns, A. Pansini, and R. Partridge, Effects of vanadium on glucose metabolism in vitro, Life Sci. 25, 1159–1164 (1979).PubMedCrossRefGoogle Scholar
  3. 3.
    Y. Shechter, Insulin-like effects of vanadium: mechanism of action, clinical and basic implications, Lett. in Peptide Sci. 5, 319–322 (1998).Google Scholar
  4. 4.
    S. Tamura, T. A. Brown, R. E. Dubler, and J. Larner, Insulin-like effect of vanadate on adipocyte glycogen synthase and on phosphorylatio of 95,000 dalton subunit of insulin receptor, Biochem. Biophys. Res. Commun. 113, 80–86 (1983).PubMedCrossRefGoogle Scholar
  5. 5.
    H. Degani, M. Gochin, S. J. D. Karlish, and Y. Shechter, Electron paramagnetic resonance studies and insulin-like effects of vanadium in rat adipocytes, Biochemistry 20, 5795–5799 (1984).CrossRefGoogle Scholar
  6. 6.
    F. H. Nielsen, Ultrace elements in nutrition, Annu. Rev. Nutr. 4, 21–41 (1984).PubMedCrossRefGoogle Scholar
  7. 7.
    J. J. Mongold, G. H. Cros, L. Vian, A. Tep, S. Ramanadham, G. Sion, et al., Toxicological aspects of vanadyl sulphate on diabetic rats: effects on vanadium levels and pancreatic B-cell morphologt, Pharmacol. Toxicol. 67, 192–198 (1990).PubMedGoogle Scholar
  8. 8.
    Y. M. Schechter and S. J. D. Karlish, Insulin-like stimulation of glucose oxidation in rat adipocytes by vanadyl (IV) ions, Nature 284, 556–558 (1980).CrossRefGoogle Scholar
  9. 9.
    C. E. Heyliger, A. G. Tahiliani, and J. H. McNeill, Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats, Science 227, 1474–1476 (1985).PubMedCrossRefGoogle Scholar
  10. 10.
    S. M. Brichard, A. M. Pottier, and J. C. Henquin, Long term improvement of glucose homeostasis by vanadate in obese hyperinsulinemic fa/fa rats, Endocrinology 125, 2510–2516 (1989).PubMedCrossRefGoogle Scholar
  11. 11.
    S. M. Brichard, C. J. Bailey, and J. C. Henguin, Marked improvement of glucose homeostasis in diabetic ob/ob mice given oral vanadate, Diabetes 39, 1326–1332 (1990).PubMedCrossRefGoogle Scholar
  12. 12.
    S. Ramanadham, G. H. Cros, J. J. Mongold, J. J. Serrano, and J. H. McNeill, Enhanced in vivo sensitivity of vanadyl-treated diabetic rats for insulin, Can. J. Physiol. Pharmacol. 68, 486–491 (1990).PubMedGoogle Scholar
  13. 13.
    J. Meyerovitch, P. Rothenberg, Y. Shechter, S. Boner-Weir, and C. R. Kahn, Vanadate normalizes hyperglycemia in two mouse models of non-insulin-dependent diabetes mellitus, J. Clin. Invest. 87, 1286–1294 (1991).PubMedCrossRefGoogle Scholar
  14. 14.
    R. U. Byerrum, Metals and their compounds in the environment, in Vanadium, E. Merian, ed., VCH, Weinheim (1991).Google Scholar
  15. 15.
    M. R. Fox, Assessment of cadmium, lead and vanadium status of large animals as related to the human food chain, J. Anim. Sci. 65, 1744–1752 (1987).PubMedGoogle Scholar
  16. 16.
    S. Okabe and T. Morinaga, Vanadium and molybdenum in the river and estuary waters which pour into the Suruga Bay, Nippon Kagaku Zasshi 89, 284–287 (1968). [in Japanese]Google Scholar
  17. 17.
    M. Iwashita, H. Ando, H. Kageyama, and T. Shimamura, Evaluation of water quality of Sagami river and its rivers analysed by ICP-MS, Bunseki Kagaku 43, 925–932 (1994) [in Japanese].Google Scholar
  18. 18.
    Y. Sakai, K. Ohshita, S. Koshimizu, and K. Tomura, Geochemical study of trace vanadium in water by preconcentrational neutron activation analysis, J. Radioanal. Nucl. Chem. 216, 203–212 (1997).CrossRefGoogle Scholar
  19. 19.
    T. Hamada, High vanadium content in Mt. Fuji groundwater and its relevance to the ancient biosphere, in Vanadium in the Environment, J. O. Nriagu, ed., Wiley, New York, pp. 97–123 (1998).Google Scholar
  20. 20.
    Y. Seko, T. Hasegawa, H. Hosaka, T. Miyazaki, and M. Sugita, Regional different in the concentration of trace elements in ground water in Yamanashi Prefecture, Biomed. Res. Trace Elements 10, 271–272 (1999) [in Japanese].Google Scholar
  21. 21.
    Y. Tsukamoto, S. Saka, K. Kumano, S. Iwanami, O. Ishida, and F. Marumo, Abnormal accumulation of vanadium in patients on chronic hemodialysis, Nephron 56, 368–373 (1990).PubMedGoogle Scholar
  22. 22.
    M. Nakamura and K. Yamada, Studies on a diabetic (KK) strain of the mouse, Diabetologin 3, 212–221 (1967).CrossRefGoogle Scholar
  23. 23.
    N. Kondo, Y. Shibayama, Y. Toyomaki, M. Yamamoto, H. Ohara, K Nakano, et al., Simple method for determination of A1c-type glycated hemoglobin(s) in rats using high performance liquid chromatography, J. Pharmacol. Methods 21, 211–221 (1989).PubMedCrossRefGoogle Scholar
  24. 24.
    R. P. Steffen, M. B. Pamnani, D. L. Clough, S. J. Huot, S. M. Muldoon, and F. J. Haddy, Effect of prolonged dietary administration of vanadate on blood pressure in the rat, Hypertension 3(Pt 2), I173-I178 (1981).PubMedGoogle Scholar
  25. 25.
    H. A. Schroeder and J. J. Balassa, Arsenic, germanium, tin and vanadium in mice: effects on growth, survival and tissue levels, J. Nutri. 92, 245–252 (1987).Google Scholar
  26. 26.
    CBEAP (Committee on Biologic Effects of Atmospheric Pollutants), Vanadium, National Academy of Sciences, Washington, DC, pp. 55–56 (1974).Google Scholar
  27. 27.
    J. L. Domingo, M. Gomez, J. M. Llobet, J. Corbella, and C. L. Keen, Improvement of glucose homeostasis by oral vanadyl or vanadate treatment in diabetic rats is accompanied by negative side effects, Pharm. Toxicol. 68, 249–253 (1991).Google Scholar
  28. 28.
    C. Zenz, Vanadium, Metals in the Environment, H. A. Waldron, ed., Academic, London, pp. 300–310 (1980).Google Scholar
  29. 29.
    K. H. Tompson, Vanadium and diabetes, BioFactors 10, 43–51 (1999).Google Scholar
  30. 30.
    A. M. Gomez-Foix, J. E. Rodriguez-Gil, C. Fillat, J. J. Guinovart, and F. Bosch, Vanadate raises fructose 2,6-biophosphate concentrations and activiates glycolysis in rat hepatocytes, Biochem. J. 255, 507–512 (1988).PubMedGoogle Scholar
  31. 31.
    J. Singh, R. C. Nordlie, and R. A. Jorgenson, Vanadate: a potent inhibitor of multifunctional glucose-6-phosphatase, Biochem. Biophys. Acta 678, 477–482 (1981).PubMedGoogle Scholar
  32. 32.
    J. A. Fagin, K. Ikejiri, and S. R. Levin, Insulinotropic effects of vanadate, Diabetes 36, 1448–1452 (1987).PubMedCrossRefGoogle Scholar
  33. 33.
    J. L. Leahy, H. E. Cooper, and G. C. Weir, Impaired insulin secretion associated with near normoglycemia: study in normal rats with 96-h in vivo glucose infusions, Diabetes 36, 459–464 (1987).PubMedCrossRefGoogle Scholar
  34. 34.
    T. Yamanouchi, H. Akabuna, F. Takaku, and Y. Akabuma, Marked depletion of plasma 1,5-anhydroglucitol, a major polyol in streptozocin-induce diabetes in rats and the effect of insulin treatment, Diabetes 35, 204–209 (1986).PubMedCrossRefGoogle Scholar
  35. 35.
    F. Umeda, T. Yamauch, H. Ishii, N. Nakashima, A. Hisatomi, and H. Nawata, Serum 1,5-anhydro-d-glucitol and glycemic control in patients with non-insulin-dependent diabetes mellitus, Tohoku J. Exp. Med. 163, 93–100 (1991).PubMedCrossRefGoogle Scholar
  36. 36.
    A. Tsuji and H. Sakurai, Vanadyl ion suppresses nitric oxide production from peritoneal macrophages of streptozotocin-induced diabetic mice, Biochem. Biophys. Res. Commun. 226, 506–511 (1996).PubMedCrossRefGoogle Scholar
  37. 37.
    J. Ramasarma and F. L. Crane, Dose vanadium play a role in cellular regulation? Curr. Topics Cell Reg. 30, 247–301 (1981).Google Scholar

Copyright information

© Humana Press Inc. 2001

Authors and Affiliations

  • Wenjun Ding
    • 1
  • Tatsuya Hasegawa
    • 1
  • Hitomi Hosaka
    • 1
  • Duan Peng
    • 1
  • Koji Takahashi
    • 2
  • Yoshiyuki Seko
    • 1
  1. 1.Department of Environment BiochemistryYamanashi Institute of Environmental SciencesYamanashiJapan
  2. 2.Japan Animal CareTokyoJapan

Personalised recommendations