Abstract
Thein vivo glucose lowering effect of orally administered inorganic vanadium compounds in diabetes was first reported in our laboratory in 1985. While both vanadate and vanadyl forms of vanadium are orally active, they are still not well absorbed. We have synthesized several organic vanadium compounds and one compound, bis(maltolato)oxovanadium(IV) or BMOV, has been extensively investigated. BMOV proved effective in lowering plasma glucose and lipids in STZ-diabetic rats when administered in drinking water over a 25 week period. The maintenance dose (0.18 mmol/kg/day) was approximately 50% of that required for vanadyl sulfate (VS). Secondary complications of diabetes were prevented by BMOV and no marked toxicity was noted. Oral gavage of STZ-diabetic rats with BMOV also reduced blood glucose levels. The ED50 for BMOV was 0.5 mmol/kg, while for VS the estimated ED50 was 0.9 mmol/kg. BMOV was also effective by the intraperitoneal route in STZ-diabetic rats. The ED50 was 0.08 mmol/kg compared to 0.22 mmol/kg for VS. Some animals treated p.o. or i.p. remained euglycemic for up to 14 weeks. An i.v. infusion of BMOV of 0.05 mmol/kg over a 30 min period reduced plasma glucose levels by 50% while VS was not effective.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Willsky GR: Vanadium in the biosphere. In: N. Dennis Chaasteen (.). Vanadium in biological systems. Kluwer Academic Publishers, Dordrecht, 1990, pp 124
Cantley LC Jr Josephson L, Warner R, Yanagisawa M, Lechene C, Guidotti G: Vanadate is a potent (Na,K)-ATPase inhibitor found in ATP derived from muscle. Journal of Biological Chemistry 252 (21) 7421–7423 1977
Nechay BR: Mechanisma of action of vanadium. Annual Review Pharmacology and Toxicology 24: 501–524, 1984
Jackson T, Salhanick AI, Sparks JD, Sparks CE, Bolognino M, Amatrude JM: Insulin-mimetic effects of vanadate in primary cultures of rat hepatocytes. Diabetes 37: 1234–1240, 1988
Duckworth WC, Solomen SS, Lipenieks J, Hamel FG, Hand S, Peavy DE: Insulin-like effects of vanadate in isolated rat adipocytes. Endoctinology 122: 2285–2289, 1988
Shechter Y, Karlish SJD: Insulin-like stimulation of glucose oxidation in rat adipocytes by vanadyl (IV) ions. Nature 284: 556–558, 1980
Tamura S, Brown TA, Whipple JH, Fujita-Yamaguchi Y, Dubler RE, Chemg K, Larner J: A novel mechanism for the insulin-like effect of vanadate on glycogen synthase in rat adipocytes. Journal of Biological Chemistry 259 (10): 6650–6658, 1984.
Tamura S, Brown TA, Dubler RE, Larner J: Insulin-like effect of vanadate on adipocyte glycogen synthase and on phosphorylation of 95,000 dalton subunit of insulin receptor. Biochem Biophys Research Communication 113: 8042, 1983
Klarlund JK: Transformation of cells by an inhibitor of phosphatases acting on phosphotyrosineinproteins. Cell 4: 707–711, 1985
Mooney RA, Bordwell KL, Luhowsky S, Casnellie JE: The insulin-like effect of vanadate on lipolysis in rat adiposytes is not accompanied by an insulin-like effect on tyrosine phosphorylation. Endocrinology 124: 422–429, 1989
Bernier M, Laird DM, Lane MD: Effect of vanadate on the cellular accumulation of pp15, an apparent product of insulin receptor tyrosine kinase activity. Journal of Biological Chemistry 263 (27): 13626–13634, 1988
Fantus EG, Kadota S, Deragon G, Foster B, Posner B: Pervanadate [peroxide(s) of vanadate] mimics insulin action in rat adipbocytes via activation of the insulin receptor tyrosine kinase. Biochemistry 28: 8864–8871, 1989
Junod A, Lambert AE, Stauffacher W, Renold AE: Diabetogenic action of streptozotocin: relationship of dose to metabolic response. Jounal of Clinical Investigation 48: 2129–2139, 1969
Kaufmann F, Rodriguez RR: Subtotal pancreatectomy in five different rat strains: incidence and course of development of diabetes. Diabetologia 27: 38–43, 1984
Nakhooda AF, Like AA, Chappel CI, Murray FT, Marilss EB: The spontaneously diabetic Wistar rat; metabolic and morphologic studies. Diabetes 26: 100–112, 1977
Nakhooda AF, Like AA, Marliss EB: Diabetes mellitus in the ‘BB’ Wistar rat. In: E.J. Andrews, B.C. Ward and N.H. Altman (eds). Spontaneous Animal Models of Human Disease Volume 1, Academic Press, Toronto, 1979, pp 131–136
Ramanadham S, Mongold JJ, Brownsey RW, Cros GH, McNeill JH: Oral vanadyl sulfate in the treatment of diabetes mellitus in rats. American Joumal of Physiology 257: H904-H911, 1989a
Rossetti L, Giaccari A, Klein-Robbenhaar E, Vogel LR: Insulinomimetic properties of trace elements and characterization of theirin vivo mode of action. Diabetes 39: 1243–1250, 1990
Battell ML, Yuen VG, McNeill JH: Treatment of BB rats with vanadyl sulfate. Pharmacological Communications 1 (4): 291–301, 1992
Cam MC, Pederson RA, Brownsey RW, McNeill JH: Long-term effectiveness of oral vanadyl sulfate in streptozotocin-diabetic rats. Diabetologia 36: 218–224, 1993a
Brichard SM, Pattier AM, Henquin JC: Long term improvement of glucose homeostatis by vanadate in obese hyperinsulinemic fa/fa rats. Endocrinology 126: 2510–2516, 1989
Brichard SM, Bailey CJ, Henquin JC: Marked improvement of glucose homeostasis in diabetic ob/ob mice given oral vanadate. Diabetes 39: 1326–1332, 1990
Blondel O, Simon J, Shevalier B, Portha B: Impaired insulin action but normal insulin receptor activity in diabetic rat liver: effect of vanadate. American Joumal of Physiology 258 (Endocrinol Metab 21): E459-E467, 1990
Heyliger CE, Tahiliani AG, McNeill JH: Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science 227: 1474–1477, 1985
Roschin AV, Ordizhonidze EK, Shalganova IV: Vanadium-toxicity, metabolism, carrier state. Jour Hyg Epid Microbiol Immunol 24: 377–383, 1980
Ramanadham S, Brownsey RW, Cros GH, Mongold JJ, McNeill JH: Sustained prevention of myocardial abnormalities in diabetic rats following withdrawal from oral vanadyl treatment Metabolism 38: 1022–1028, 1989b
Pederson RA, Ramanadham S, Buchan AMJ, McNeill JH: Long-term effects of vanadyl treatment on streptozocin-induced diabetes in rats. Diabetes 38: 1390–1395, 1989
Cam MC, Faun J, McNeill JH: Concentration-dependent glucose-lowering effects of oral vanadyl are maintained following treatment withdrawal in streptozotocin diabetic rats. Metabolism 1994 (in press)
Dai S, Thompson KH, McNeill JH: One-year treatment of streptozotocin-induced diabetic rats with vanadyl sulphate. Pharmacology and Toxicology 74: 101–109, 1994a
Dai S, McNeill JH: One-year treatment of non-diabetic and streptozotocin-diabetic-rats with vanadyl sulphate did not alter blood pressure or haematological indices. Pharmacology and Toxicology 74: 110–115 1994b
Rocchini AP: Is insulin resistance in hypertension a generalized phenomena? In: U. Smith, N.E. Bruun, T. Hedner and B. Hokfelt (eds). Hypertension is an insulin resistant disorder: genetic factors and cellular mechanisms. Excerpta Medica, 1992, pp 213–225
Reaven GM, Chang H: Relationship between blood pressure, plasma insulin and triglyceride concentration and insulin action in spontaneously hypertensive and Wistar Kyoto rats. American Journal of Hypertension 4: 34–38, 1991
Reaven GM, Chang H, Hoffman BB, Azhar S: Resistance to insulin stimulated glucose uptake in adipocytes isolated from spontaneously hypertensive rats. Diabetes 38: 1155–1160, 1989
Buchanan TA, Youn JH, Campese VM, Sipos GF: Enhanced glucose tolerance in spontaneously hypertensive rats: pancreatic β-cell hyperfunction with normal insulin sensitivity. Diabetes 41: 872–878, 1992
Bhanot S, McNeill JH: Vanadyl sulfate lowers plasma insulin and blood pressure in spontaneously hypertensive rats. Hypertension 24: 625–632, 1994a
Hwang IS, Ho H, Hoffman BB, Reaven GM: Fructose induced insulin resistance and hypertension in rats. Hypertension 10: 512–516, 1987
Bhanot S, McNeill JH, Bryer-Ash M: Vanadyl sulfate prevents fuctose-induced hyperinsulinemia and hypertension in rats. Hypertension 23: 308–312, 1994b
Conklin AW, Skinner CS, Feltin TL, Sanders CL: Clearance and dismibution of intratracheally instilled vanadium-48 compounds in the rat. Toxicological Letters 11: 199–203, 1982
Underwood EJ: Vanadium In: Trace elements in human and animal nutrition. Academic Press, New York, 1977, pp 388–397
Cam MC, Cros GH, Serrano JJ, Lazaro R, McNeill JH:In vivo antidiabetic actions of naglivan, an organic vanadyl compound in streptozotocin-induced diabetes. Diabetes Research and Clinical Practice 20: 111–121, 1993b
McNeill JH, Yuen VG, Hoveyda HR, Orvig C: Bis(maltolato) oxovanadium(IV) is a potent insulin mimic. Journal of Medicinal Chemistry 35 (8): 1489–1492, 1992
Yuen VG, Orvig C, Thompson KH, McNeill JH: Improvement in cardiac dysfunction in streptozotocin-induced diabetic rats following chronic oral administration of bis(maltolato)oxovanadium(IV). Canadian Journal of Physiology and Pharmacology 71: 270–276, 1993a
Dai S, Yuen VG, Orvig C, McNeill JH: Prevention of diabetes-induce pathology in STZ-diabetic rats by bis(maltolato)oxovanadium(JV). Pharmacological Communications 3 (4): 311–321, 1993
Yuen VG, Orvig C, McNeill JH: Glucose-lowering effects of a new organic vanadium complex, bis(maltolato)oxovanadium(IV). Canadian Journal of Physiology and Pharmacology 71: 263–269, 1993b
Yuen VG, Orvig C, McNeill JH: Comparison of the glucose lowering properties of vanadyl sulfate and bis(maltolato)oxovanadium(IV) following acute and chronic administration. Canadian Journal of Physiology and Pharmacology 73: 55–64, 1995
Bhanot S, Bryer-Ash M, Cheung A, McNeill JH: Bis(maltolato)oxovanadium(IV) attenuates hyperinsulinemia and hypertension in spontaneously hypertensive rats. Diabetes 43: 857–861, 1994c
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
McNeill, J.H., Yuen, V.G., Dai, S. et al. Increased potency of vanadium using organic ligands. Mol Cell Biochem 153, 175–180 (1995). https://doi.org/10.1007/BF01075935
Issue Date:
DOI: https://doi.org/10.1007/BF01075935