Abstract
Vanadium has been shown to be beneficial in the oral treatment of animal models of type 1 and type 2 diabetes. The aim of the study was to evaluate the short‐term effects of sodium metavanadate in prediabetic BB‐DP rats. To do this, 96 rats were divided into 4 equal groups. Groups VI, V2, V3 were treated with sodium metavanadate (0.1, 0.2 and 0.3 mg/ml respectively) and sodium chloride (0.5 mg/ml) in drinking water for 7 days. Group C received only sodium chloride (0.5 mg/ml). Blood glucose (BG), glycosuria, ketonuria, body weight and insulinemia were determined. The age of onset of diabetes was significantly higher for groups V2, V3 compared to group C, (p < 0.05) and depends on the metavanadate concentration (V3 vs. V1, p=0.006). The incidence of diabetes was lower in the rats treated with metavanadate than in the control group, but this difference was not statistically significant. In diabetic rats, the BG at the onset was higher in group C than in groups V, p < 0.05. Insulinemia, at the onset of the treatment as well as immediately after its cessation showed a drop in the treatment groups, proportionally to the dosage of vanadium, but later increased slowly and continuously until the end of the experiment. In conclusion, metavanadate delays the development of diabetes in BB‐DP rats, but does not prevent its onset. A milder form of diabetes occurs in diabetic rats treated with metavanadate. The effects depend on the metavanadate concentration and 0.2 mg/ml is preferable.
Keywords: type 1 diabetes, sodium metavanadate, BB‐DP rats, insulin‐mimetic, prevention, beta‐cells
References
- 1. Cheta D.M., Preventing Diabetes, Theory, Practice and New Approaches, Wiley, Chichester , 1999. [Google Scholar]
- 2. Cheta D., Orasanu G., Prevention of type 1 diabetes in animal models In: Cheta D. ed., New Insights into Experimental Diabetes, The Publishing House of the Romanian Academy, Bucharest , 2002, pp. 362–403. [Google Scholar]
- 3. McNeill J.H., Yuen V.G., Hoveyda H.R., Orvig C., Bis(maltolato)oxovanadium (IV) is a potent insulin mimic, J. Med. Chem., 35: 1489–1491, 1992. [DOI] [PubMed] [Google Scholar]
- 4. Ramanadham S., Brownsey R. W., Cros G.H., Mongold J.J., McNeill J.H., Sustained prevention of myocardial and metabolic abnormalities in diabetic rats following withdrawal from oral vanadyl treatment, Metabolism, 38: 1022–1028, 1989. [DOI] [PubMed] [Google Scholar]
- 5. Morinville A., Maysinger D., Shaver A., From vanadis to atropos: vanadium compounds as pharmacological tools in cell death signaling, Trends Pharmacol. Sci., 19: 452–460, 1998. [DOI] [PubMed] [Google Scholar]
- 6. Dai S., Thompson K.H., Vera E., McNeill J.H., Toxicity studies on one‐year treatment of non‐diabetic and streptozotocin diabetic rats with vanadyl sulphate, Pharmacol. & Toxicol., 75: 265–273, 1994. [DOI] [PubMed] [Google Scholar]
- 7. Brichard S.M., Henquin J.C., The role of vanadium in the management of diabetes, Trends Pharmacol. Sci., 16: 265–270, 1995. [DOI] [PubMed] [Google Scholar]
- 8. Li S.H., McNeill J.H., In vivo effects of vanadium on GLUT4 translocation in cardiac tissue of STZ‐diabetic rats, Mol. Cell. Biochem., 217: 121–129, 2001. [DOI] [PubMed] [Google Scholar]
- 9. Wang J., Yuen V.G., McNeill J.H., Effect of vanadium on insulin and leptin in Zucker diabetic fatty rats, Mol. Cell. Biochem., 218: 93–96, 2001. [DOI] [PubMed] [Google Scholar]
- 10. Shafrir E., Spielman S., Nachliel I., Khamaisi M., Bar‐On H., Ziv E., Treatment of diabetes with vanadium salts: general overview and amelioration of nutritionally induced diabetes in the Psammomys obesus gerbil, J. Clin. Endocrinol. Metab., 86: 1410–1417, 2001. [DOI] [PubMed] [Google Scholar]
- 11. Posner B.I., Peroxovanadium compounds: potent PTP inhibitors with insulin‐like effects [Abst.], The EASD Satellite Symposium, Sitges, Barcelona, 9: 2000.
- 12. Cam M.C., Rodrigues B., McNeill J.H., Distinct glucose lowering and beta cell protective effects of vanadium and food restriction in streptozotocin‐diabetes, Eur. J. Endocrinol., 141: 546–554, 1999. [DOI] [PubMed] [Google Scholar]
- 13. Sekar N., Li J., Shechter Y., Vanadium salts as insulin substitutes: mechanism of action, a scientific and therapeutic tool in diabetes mellitus research, Crit. Rev. Biochem. Mol. Biol., 31: 339–359, 1996. [DOI] [PubMed] [Google Scholar]
- 14. Vlahos W.D., Seemayer T.A., Yale J.F., Diabetes prevention in BB rats by inhibition of endogenous insulin secretion, Metabolism, 40: 825–829, 1991. [DOI] [PubMed] [Google Scholar]
- 15. Meyerovitch J., Waner T., Sack J., Kopolovic J., Shemer J., Attempt to prevent the development of diabetes in non‐obese diabetic mice by oral vanadate administration, Isr. Med. Assoc. J., 2: 211–214, 2000. [PubMed] [Google Scholar]
- 16. Blondel O., Bailbe D., Portha B., In vivo insulin resistance in streptozotocin diabetic rats ‐ evidence for reversal following oral vanadate treatment, Diabetologia, 32: 185–190, 1989. [DOI] [PubMed] [Google Scholar]
- 17. Brichard S.M., Okitolonda W., Henquin J.C., Long term improvement of glucose homeostasis by vanadate treatment in diabetic rats, Endocrinology, 123: 2048–2053, 1988. [DOI] [PubMed] [Google Scholar]
- 18. Yilmaz M.T., The remission concept in type 1 diabetes and its significance in immune intervention, Diabetes. Metab. Rev., 9: 337–348, 1993. [DOI] [PubMed] [Google Scholar]
- 19. Sprietsma J.E., Schuitmaker G.E., Diabetes can be prevented by reducing insulin production, Med. Hypotheses, 42: 15–23, 1994. [DOI] [PubMed] [Google Scholar]
- 20. Cam M.C., Li W.M., McNeill J.H., Partial preservation of pancreatic beta‐cells by vanadium: evidence for long‐term amelioration of diabetes, Metabolism, 46: 769–778, 1997. [DOI] [PubMed] [Google Scholar]
- 21. Dai S., Thompson K.H., McNeill J.H., One year treatment of streptozotocin‐induced diabetic rats with vanadyl sulphate, Pharmacol. & Toxicol., 75: 101–109, 1994. [DOI] [PubMed] [Google Scholar]
- 22. Cam M.C., Brownsey R.W., McNeill J.H., Mechanisms of vanadium action: insulin‐mimetic or insulin‐enhancing agent?, Can. J. Physiol. Pharmacol., 78: 829–847, 2000. [PubMed] [Google Scholar]
- 23. Brichard S.M., Desbuquois B., Girard J., Vanadate treatment of diabetic rats reverses the impaired expression of genes involved in hepatic glucose metabolism: effects on glycolytic and gluconeogenic enzymes and on glucose transporter GLUT2, Mol. Cell. Endocrinol., 91: 91–97, 1993. [DOI] [PubMed] [Google Scholar]
- 24. Mosseri R., Waner T., Shefi M., Shafrir E., Meyerovitch J., Gluconeogenesis in non‐obese diabetic (NOD) mice: in vivo effects of vanadate treatment on hepatic glucose‐6‐phoshatase and phosphoenolpyruvate carboxikinase, Metabolism, 49: 321–325, 2000. [DOI] [PubMed] [Google Scholar]
- 25. Ramachandran B., Kandaswamy M., Narayanan V., Subramanian S., Insulin mimetic effects of macrocyclic binuclear oxovanadium complexes on streptozotocininduced experimental diabetes in rats, Diabetes. Obes. Metab., 5: 455–461, 2003. [DOI] [PubMed] [Google Scholar]
- 26. Cusi K., Cukier, S. DeFronzo, R.A. , Torres M., Puchulu F.M., Redondo J.C., Vanadyl sulfate improves hepatic and muscle insulin sensitivity in type 2 diabetes, J. Clin. Endocrinol. Metab., 86: 1410–1417, 2001. [DOI] [PubMed] [Google Scholar]
- 27. Meyerovitch J., Rothenberg P., Shechter Y., Bonner‐Weir S., Kahn KR., Vanadate normalizes hyperglycemia in two mouse models of non‐insulin dependent Diabetes Mellitus, J. Clin. Invest., 87: 1286–1294, 1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Wang J., Yuen V.G., McNeill J.H., Effect of vanadium on insulin and leptin in Zucker diabetic fatty rats, Mol. Cell. Biochem., 218: 93–96, 2001. [DOI] [PubMed] [Google Scholar]
- 29. Malabu V.H., Dryden S., McCarthy H.D., Killpatrick A., Williams G., Effects of chronic vanadate administration in the STZ‐induced diabetic rat. The antihyperglycemic action of vanadate is attributable entirely to its suppression of feeding, Diabetes, 43: 1267–1270, 1994. [DOI] [PubMed] [Google Scholar]
- 30. Conconi M.T., DeCarlo E., Vigolo S., Grandi C., Bandoli G., Sicolo N., Tamagno G., Parnigotto P.P., Nussdorfer G.G., Effects of some vanadyl coordination compounds on the in vitro insulin release from rat pancreatic islets, Horm. Metab. Res., 35: 402–406, 2003. [DOI] [PubMed] [Google Scholar]
- 31. Meyerovitch J., Farfel Z., Sack J., Shechter Y., Oral administration of vanadate normalizes blood glucose levels in streptozotocin‐treated rats: characterization and mode of action, J. Biol. Chem., 262: 6658–6662, 1987. [PubMed] [Google Scholar]