Summary
Recent studies have demonstrated the insulin-like effects of oral vanadyl sulphate in the streptozotocin-diabetic rat, including the amelioration of hyperglycaemia and the prevention of diabetes-related cardiac and adipose tissue dysfunction. However, the possibility that vanadyl treatment, routinely initiated at 3 days after the induction of diabetes, had prevented the full cytotoxic destruction of the beta cell, and thus accounted for the apparent anti-diabetic properties of vanadyl was questioned. Hence in the present study, we examined the effectiveness of vanadyl sulphate as a glucose-lowering and anti-diabetic agent when administration was delayed from the time of induction of diabetes. Male Wistar rats were injected with a single intravenous dose of streptozotocin (55 mg/kg). Vanadyl sulphate was administered in the drinking water at a concentration of 0.75 mg/ml from 3, 10 and 17 days after the streptozotocin injection and treatment was then maintained for 5 months. Vanadyl intake was accompanied by lowered serum levels of triglyceride and cholesterol with no associated enhancement in circulating insulin. Vanadyl-treated diabetic animals showed improved glucose tolerance while insulin release in vivo was still markedly lower than in non-diabetic rats. Adipose tissue function, as expressed by basal and epinephrine-stimulated lipolysis in isolated adipose tissue, was also normalized in vanadyl-treated diabetic animals. These responses were all observed whether vanadyl treatment was initiated 3, 10 or 17 days after induction of diabetes. Finally, prolonged treatment with vanadyl sulphate (in this case up to 5 months) did not cause any apparent hepatic toxicity as assessed histologically. Diabetes-induced morphological changes in the kidney were also prevented by vanadyl treatment. Thus, these findings support the concept that the efficacy of vanadyl treatment is unrelated to protection from the acute toxic effects of streptozotocin on pancreatic beta cells. Further, these studies provide additional support for the notion suggested in earlier studies that either improved pancreatic function may result from the alleviation of hyperglycaemia by vanadium treatment or that some residual pancreatic function which in itself is insufficient to prevent the onset and progression of the diabetic state may contribute to an effective response to administered vanadium.
Article PDF
Similar content being viewed by others
References
Dubyak GR, Kleinzeller A (1980) The insulin-mimetic effects of vanadate in isolated rat adipocytes. Dissociation from effects of vanadate as a (Na+-K+)-ATPase inhibitor. J Biol Chem 255: 5306–5312
Schecter Y, Karlish SJD (1980) Insulin-like stimulation of glucose oxidation in rat adipocytes by vanadyl (IV) ions. Nature 284: 556–558
Clark AS, Fagan JM, Mitch WE (1985) Selectivity of the insulinlike actions of vanadyl on glucose and protein metabolism in skeletal muscle. Biochem J 232: 273–276
Duckworth WC, Solomon SS, Liepnieks J, Hamel FG, Hand S, Peavy DE (1988) Insulin-like effects of vanadate in isolated rat adipocytes. Endocrinology 122: 2285–2289
Schecter Y, Ron A (1986) Effect of depletion of phosphate and bicarbonate ions on insulin action in rat adipocytes. J Biol Chem 261: 14945–14950
Heyliger CE, Tahiliani AG, McNeill JH (1985) Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science 227: 1474–1477
Ramanadham S, Mongold JJ, Brownsey RW, Cros GH, McNeill JH (1989) Oral vanadyl sulphate in the treatment of diabetes mellitus in the rat. Am J Physiol 257: H904-H911
Ramanadham S, Cros GH, Mongold JJ, Serrano JJ, McNeill JH (1990) Enhanced in vivo sensitivity of vanadyl-treated diabetic rats to insulin. Can J Physiol Pharmacol 68: 486–491
Tamura S, Brown TA, Dubler RE, Larner J (1984) Insulin-like effect of vanadate on adipocyte glycogen synthase and on phosphorylation of 95,000 dalton subunit of insulin receptor. Biochem Biophys Res Commun 113: 80–86
Bernier M, Laird DM, Lane MD (1988) Effect of vanadate on the cellular accumulation of pp15, an apparent product of insulin receptor tyrosine kinase action. J Biol Chem 263: 13525–13534
Cordera R, Andraghetti G, DeFronzo RA, Rossetti L (1990) Effect of in vivo vanadate treatment on insulin receptor tyrosine kinase activity in partially pancreatectomized diabetic animals. Endocrinology 126: 2177–2183
Fantus EG, Kadota S, Deragon G, Foster B, Posner B (1989) Pervanadate [Peroxide(s) of vanadate] mimics insulin action in rat adipocytes via activation of the insulin receptor tyrosine kinase. Biochemistry 28: 8864–8871
Green A (1986) The insulin-like effect of sodium vanadate on adipocyte glucose transport is mediated at a post insulin-receptor level. Biochem J 238: 663–669
Strout HV, Vicario PP, Saperstein R, Slater EE (1989) The insulin-mimetic effect of vanadate is not correlated with insulin receptor tyrosine kinase activity nor phosphorylation in mouse diaphragm in vivo. Endocrinology 124: 1918–1924
Ramanadham S, Brownsey RE, Cros GH, Mongold JJ, McNeill JH (1989) Sustained prevention of myocardial and metabolic abnormalities in diabetic rats following withdrawal from oral vanadyl treatment. Metabolism 38: 1022–1028
Pederson RA, Ramanadham S, Buchan AMJ, McNeill JH (1989) Long-term effects of vanadyl treatment on streptozotocin-induced diabetes in rats. Diabetes 38: 1390–1395
Obih P, Wingard M, Olubadewo J (1992) Effectiveness of alzet minipump administration of vanadyl sulphate in prevention of STZ-induced diabetes. FASEB J 6: A1591 (Abstract)
Pederson RA, Buchan MAJ, Zahedi AS, Chan CB, Brown JC (1982) Effect of jejunoileal bypass on the enteroinsular axis. Regulatory Peptides 5: 53–63
Mongold JJ, Cros GH, Vian L et al. (1990) Toxicological aspects of vanadyl sulphate treatment of diabetic rats. Pharmacol Toxicol 67: 192–198
McNeill JH, Cam MC, Pederson R, Faun J (1991) Vanadyl sulphate has prolonged insulin-like effects in the streptozotocin-diabetic rat. FASEB J 5: A1311 (Abstract)
Bendayan M, Gringas D (1989) Effect of vanadate administration on blood glucose and insulin levels as well as on the exocrine pancreatic function in streptozotocin-diabetic rats. Diabetologia 32: 561–567
Brichard SM, Okitolonda W, Henquin JC (1988) Long term improvement of glucose homeostasis by vanadate treatment in diabetic rats. Endocrinology 123: 2048–2053
Blondel O, Bailbe D, Portha B (1989) In vivo insulin resistance in streptozotocin-diabetic rats — evidence for reversal following oral vanadate treatment. Diabetologia 32: 185–910
Junod A, Lambert AE, Orci L, Pictet R, Gonet AE, Renold AE (1967) Studies of the diabetogenic action of streptozotocin. Proc Soc Exp Biol Med 126: 201–205
Rossetti L, Laughlin MR (1989) Correction of chronic hyperglycemia with vanadate, but not with phlorizin, normalizes in vivo glycogen repletion and in vitro glycogen synthase activity in diabetic skeletal muscle. J Clin Invest 84: 892–899
Leahy JL, Weir GC (1991) Beta-cell dysfunction in hyperglycaemic rat models: recovery of glucose-induced insulin secretion with lowering of the ambient glucose level. Diabetologia 34: 640–647
Serradas P, Bailbe D, Blondel O, Portha B (1990) Abnormal B-cell function in rats with non-insulin-dependent diabetes induced by neonatal streptozotocin: effect of in vivo insulin, phlorizin, or vanadate treatments. Pancreas 6: 54–62
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cam, M.C., Pederson, R.A., Brownsey, R.W. et al. Long-term effectiveness of oral vanadyl sulphate in streptozotocin-diabetic rats. Diabetologia 36, 218–224 (1993). https://doi.org/10.1007/BF00399953
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00399953