Abstract
Vanadium (V) is an orally effective treatment for diabetes, but relatively little is known about the mechanisms controlling its normal metabolism nor the long term pharmacokinetics of oral administration. We have examined the accumulation of V in various organs from rats fed liquid diet for up to 18 days, containing no additional V, 1.6, 80, or 160 μmole/kg/day as either sodium orthovanadate (SOV) or vanadyl sulfate (VS). V content was assayed using a sensitive neutron activation analysis method. The organs of the nonsupplemented animals contained widely varying concentrations (ng of V/g dry tissue weight) with brain < fat < blood < heart < muscle < lung < liver < testes < spleen < kidney. All organs accumulated V in a dose dependent manner. Not all organs showed steady state amount of V at 18 days, so additional rats were fed SOV or VS, switched to control diet, and assayed at 0, 4 and 8 days. From this data we calculated organ half lives of V. Insulin sensitive tissue tissues, such as liver and fat, had shorter half-lives than tissues that are relatively less insulin sensitive, such as spleen, brain and testes. SOV and VS fed rats showed similar patterns, but VS had somewhat shorter t1/2's. Additional studies of old and young rats fed control diet for 45 days show accumulation of V in spleen and testes. These results indicate that vanadium metabolism varies widely among different organs, and that insulin, either directly or indirectly has effects on the retention of vanadium. This may have impact on the therapeutic use of vanadium in Type I diabetics with no insulin, or Type II patients who may be relatively hyperinsulinemic.
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References
Nielsen F, Uthus E: The essentiality and metabolism of vanadium. In: N.D. Chasteen (ed.). Vanadium in Biological Systems. Kluwer Academic Publishers, Dordrecht, p. 51–62, 1990
Nielsen F: Nutritional requirements for boron, silicon, vanadium, nickel and arsenic: Current knowledge and speculation. Biological and Trace Element Research. 26(27):599–611, 1990
Nielsen F: Nutritional requirements for boron, silicon, vanadium, nickel, and arsenic: Current knowledge and speculation. FASEB 5(12):2661–2667, 1991
Neve J: Clinical implications of trace elements in endocrinology. Biological and Trace Element Research 32:173–185, 1992
McKeehan W, McKeehan K, Hammond S, Ham R: Improved medium for clonal growth of human diploid fibroblasts at low concentrations of serum protein. In Vitro 3:399–416, 1977
Carpenter G, Vanadate EGF: The stimulation of DNA synthesis. Biochem Biophys Res Communications. 102:1115–1121, 1981
Mountjoy K, Flier J: Vanadate regulates glucose transporter (Glut-1) expression in NIH3T3 mouse fibroblasts. Endocrinology 127(4): 2025–2034, 1990
Smith J: Vanadium ions stimulate DNA synthesis in Swiss mouse 3T3 and 3T6 cells. PNAS 80:6162–6166, 1983
Canalis E: The effect of sodium vanadate on deoxyribonucleic acid and protein synthesis in cultured rat calvaraie. Endocrinology 116: 855–862, 1985
Kato Y, Iwamoto M, Koike T, Suzuki F: Effect of vanadateoncartilagematrix proteoglycan synthesis in rabbit costal chondrocyte cultures. Journal of Cell Biology. 104:311–319, 1987
Lau K, Tanimoto H, Baylink D: Vanadate stimulates bone cell proliferation and bone collagen synthesis in vitro. Endocrinology 123:2858–2867, 1988
Nechay B, Norcross-Nechay K, Nechay P, Jena D: Presented at the Spurenelement Symposium, 1989
Shechter Y: Insulin-mimetic effects of vanadate Possible implications for future treatmentof diabetes. Diabetes 39(1):1–5, 1990
Robertson R, Klein O: Treatment of diabetes mellitus. Diabetologia 35(Sup. 2):S8-S17, 1992
Brichard S, Lederer J, Henquin J: The insulin-like properties of vanadium: A Curiosity or a perspective for the treatment of diabetes? Diabetes Metabolism. 17(5):435–440, 1991
Vialettes B, Silvestre P: Pharmacological approach in the treatment of insulin resistance. Horm Res 38(1–2):51–56, 1992
Shechter Y, Shisheva A: Vanadium salts and the future treatment of diabetes. Endeavour 17(1):27–31, 1993
Heyliger C, Tahiliani A, McNeill J: Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science 227:1474–1477, 1985
Meyerovitch J, Farfel Z, Sack J, Schechter Y: Oral administration of vanadate normalizes blood glucose levels in streptozotocin-treated rats: Characteristics and mode of action. Journal of Biological Chemistry 262:6658–6662, 1987
Blondel O, Bailbe D, Portha B:In vivo insulin resistance in streptozotocin-diabetic rats: Evidence for reversal following oral vanadate treatment. Diabetologia. 32(3):185–190, 1989
Brichard, S., Okitolonda, W., and Henquin, J.: Long term improvement of glucose homeostasis by vanadate treatment in diabetic rats. Endocrinology. 123(4):2048–2053, 1988
Ramanadham S, Mongole J, Brownsey R, Cros G, MeNeill J: Oral vanadyl sulfate in the treatment of diabetes mellitus in rats. Am J Physiol 257(3):H904–911, 1989
Pederson, R, Ramanadham, S., Buchan, A., and McNeill, J: Longterm effects of vanadyl treatment on streptozotocin-induced diabetes in rats. Diabetes. 38(11):1390–1395, 1989
Ramanadham S, Brownsey R, Cros G, Mongold J, McNeill J: Sustained prevention of myocardial and metabolic abnormalities in diabetic rats following withdrawal from oral vanadyl treatment. Metabolism. 38(10):1022–1028, 1989
Sakurai H, Tsuchiya K, Nukatsuke M, Sofue M, Kawada J: Insulin-like effect of vanadyl ion on streptozotocin-induced diabetic rats. J. Endocrinol. 126(3):451–459, 1990
Ramanadham S, Cros G, Mongold J, Serrano J, McNeill J: Enhanced in vivo sensitivity of vanadyl-treated diabetic rats to insulin. Can J Physiol-Pharmacol 68(4):486–491, 1990
Venkatesan N, Avidan A, Davidson M: Antidiabetic action of vanadyl in rats independent of in vivo insulin-receptor kinase activity. Diabetes 40(4):492–498, 1991
Ozansoy G, Karasu C, Ozcelikay A: The effect of oral vanadyl treatment on the reactivity of tracheal smooth muscle obtained from insulin dependent diabetic rats. Gen Pharmacol 24(1):115–119, 1993
Domingo J, Gomez M, Llobet J, Corbella J, Keen C: Oral vanadium administration to streptozotocin-diabetic rats has marked negative side-effects which are independent of the form of vanadium used. Toxicology 66(3):279–287, 1991
Domingo J, Gomez M, Llobet J, Corbella J, Keen C: Improvement of glucose homeostasis by oral vanadyl or vanadate treatment in diabetic rats is accompanied by negative side effects. Pharmacology-Toxicology 68(4):249–253, 1991
Sanchez D, Ortega A, Domingo J, Corbella J: Developmental toxicity evaluation of orthovanadate in the mouse. Biological and Trace Element Research 30:219–226, 1991
Llobet J, Colomina M, Sirvent J, Domingo J, Corbella J: Reproductivetoxicity evaluation of vanadium in mab mice. Toxicology 80:199–206, 1993
Leonard A, Gerber G: Mutagenicity, carcinogenicity and terato genicity of vanadium compounds. Mutation Research 317(1):81–88, 1994
Cohen, M., Wei, C., Tom, H., and Kao, K. Effect of ammonium meta vanadate on the murine immune response. J Tox Envir Health 19: 279–288, 1986
Cohen M, Chen C, Wei C: Decreased resistance toListeria monocytogenes in mice following vanadate exposure and effects upon the function of macrophages. Int J Immunopharmac 11:185–292, 1989
Wang E, Choppin P: Effect of vanadate on intracellular distribution and function of 10 nm filaments. Proc Natl Acad Sciences USA 78: 2363–2367, 1981
Cohen M, Wei C: Effects of ammonium metavanadate treatment upon macrophage glutations redox cycle activity, superoxide production, and intracellular glutation status. J Leukocyte Biol 44:122–129, 1988
Cohen M, Parsons E, Schlesinger R, Zelikoff J: Immunotoxicity ofin vitro vanadium exposures: Effects on interleukin-1, tumor necrosis factor-α and prostaglandin E2 production by WEHI-3 macrophages. Int J Immunopharmac 15(3):437–446, 1993
Blotcky AJ, Duckworth WC, Ebrahim A, Hamel FG, Rack EP, Sharma RB: Determination of vanadium in serum by pre-irradiation and post-irradiation chemistryand neutron activation analysis. Journal of Radioanalytical and Nuclear Chemistry. 134(1):151–160, 1989
Peavy DE, Edmondson JW, Duckworth WC: Selective effects of inhibitors of hormone processing on insulin action in isolated hepatocytes. Endocrinology 114:753–760, 1984
World Health Organization. International Programme on Chemical Safety, Environmental Health Criteria 81 Vanadium 1988
Hamel F, Solomon S, Jespersen A, Blotcky A, Rack E, Duckworth W: Alteration of tissue vanadium content in diabetes. Metabolism 42(12):1503–1505, 1993
Shisheva A, Ikonomow O, Schechter Y: The Protein tyrosine phosphatase inhibitor, pervanadate, is powerful antidiabetic agent in streptozotocin-treated diabetic rats. Endocrinology 134(1):507–10, 1994
Posner BI, Faure R, Burgess JW, Bevan AP, Lachance D, Zhang-Sun G, Fantus IG, Ng, JB, Hall DA, Lum BS: Peroxovanadium compounds. A new class of potent phosphotyrosine phosphatase inhibitors which are insulin mimetics. J Biol Chem 269(6): 4596–4604, 1994
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). Can J Physiol Pharmacol 71(3–4):270–276, 1993
Yuen V, Orvig C, McNeill J: Glucose-lowering effects of a new organic vanadium complex, bis(maltolato) oxovanadium (IV). Can J Physiol Pharmacol 71(3–4):263–269, 1993
Cam M, Cros G, Serrano J, Lazaro R, McNeill J:In vivo antidiabetic actions of naglivan, an organic vanadyl compound in streptozotocin-induced diabetes. Diabetes Res Clin Pract 20(2):111–121, 1993
D'Onofrio F, Le MQ, Chiasson JL, Srivastava AK: Activation of mitogen activated protein (MAP) kinases by vanadate is independent of insulin receptor autophosphorylation. FEBS Letters 340(3): 269–75, 1994
Shisheva A, Shechter Y: Mechanism of Pervanadate stimulation and potentiation of insulin-activated glucose transport in rat adipocytes: Dissociation from vanadate effect. Endocrinology 133(4):1334–1562, 1993
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Hamel, F.G., Duckworth, W.C. The relationship between insulin and vanadium metabolism in insulin target tissues. Mol Cell Biochem 153, 95–102 (1995). https://doi.org/10.1007/BF01075923
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DOI: https://doi.org/10.1007/BF01075923