Abstract
Diabetes is a metabolic disorder characterized by elevated blood glucose levels. Although conventional treatments such as insulin and other drugs reduce blood glucose, there is still a therapeutic need for effective orally administered drugs. Trace elements like vanadium and tungstate have been successfully demonstrated to reduce blood glucose in experimental diabetes with minimal chronic complications. We investigated the anti-hyperglycemic effects of cobalt in streptozotocin-diabetic rats. Normal and diabetic rats were provided with drinking water containing 3.5 mM cobalt chloride for three weeks followed by 4 mM for four weeks. Body weights and fluid consumption were monitored on a daily basis, while food intake was recorded twice every week. Prior to termination, an oral glucose tolerance test was performed on the animals. Diabetic rats lost significant body weight (357 ± 2 gm) compared to controls (482 ± 3 gm). Body weight was further reduced by cobalt treatment (290 ± 2 gm). Although it was difficult to establish a dosing regimen without weight loss, food and fluid consumption in cobalt-treated diabetic rats improved significantly compared to untreated diabetics. Plasma glucose levels were significantly reduced with reference to diabetic controls (29.3 ± 0.9 mM) by the fourth week to a lower but still hyperglycemic level (13.6 ± 3.4 mM). Cobalt-treated diabetic rats demonstrated an enhanced ability to clear a glucose load compared to untreated diabetics. Cobalt treatment neither affected the feeding and drinking patterns nor plasma glucose in normoglycemic animals although body weights decreased compared to untreated controls. We conclude that chronic cobalt treatment decreases plasma glucose levels in STZ-diabetic rats and improves tolerance to glucose.
Similar content being viewed by others
References
Barbera A, Rodriguez-Gil JE, Guinovart JJ. (1994) Insulin-like actions of tungstate in diabetic rats. Normalization of hepatic glucose metabolism. J Biol Chem 269: 20047–20053
Cam MC, Pederson RA, Brownsey RW, McNeill JH. (1993) Long-term effectiveness of oral vanadyl sulphate in streptozotocin-diabetic rats. Diabetologia 36: 218–224
Clyne N, Hofman-Bang C, Haga Y et al. (2001) Chronic cobalt exposure affects antioxidants and ATP production in rat myocardium. Scand J Clin Lab Invest 61: 609–614
Eaton RP. (1972) Cobalt chloride-induced hyperlipemia in the rat: effects on intermediary metabolism. Am J Physiol 222: 1550–1557
Endoh H, Kaneko T, Nakamura H, Doi K, Takahashi E. (2000) Improved cardiac contractile functions in hypoxia-reoxygenation in rats treated with low concentration Co(2+). Am J Physiol Heart Circ Physiol 279: H2713–H2719
Kaneto H, Kajimoto Y, Miyagawa J et al. (1999) Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity. Diabetes 48: 2398–2406
McNeill JH, Battell M, Cam M et al. (1994) Oral vanadium and lowering of blood glucose. Diabetes 43: 1268–1270
Nagareddy PR, Vasudevan H, McNeill JH. (2005) Oral administration of sodium tungstate improves cardiac performance in streptozotocin-induced diabetic rats. Can J Physiol Pharmacol 83: 405–411
Nomura Y, Okamoto S, Sakamoto M, Feng Z, Nakamura T. (2005) Effect of cobalt on the liver glycogen content in the streptozotocin-induced diabetic rats. Mol Cell Biochem 277: 127–130
Pederson RA, Ramanadham S, Buchan AM, McNeill JH. (1989) Long-term effects of vanadyl treatment on streptozocin-induced diabetes in rats. Diabetes 38: 1390–1395
Saker F, Ybarra J, Leahy P et al. (1998) Glycemia-lowering effect of cobalt chloride in the diabetic rat: role of decreased gluconeogenesis. Am J Physiol 274: E984–991
Yang L, Crans DC, Miller SM et al. (2002) Cobalt(II) and cobalt(III) dipicolinate complexes: solid state, solution, and in vivo insulin-like properties. Inorg Chem 41: 4859–4871
Ybarra J, Behrooz A, Gabriel A, Koseoglu MH, Ismail-Beigi F. (1997) Glycemia-lowering effect of cobalt chloride in the diabetic rat: increased GLUT1 mRNA expression. Mol Cell Endocrinol 133: 151–160
Yildirim O, Buyukbingol Z. (2002) Effects of supplementation with a combination of cobalt and ascorbic acid on antioxidant enzymes and lipid peroxidation levels in streptozocin-diabetic rat liver. Biol Trace Elem Res 90: 143–154
Yildirim O, Buyukbingol Z. (2003) Effect of cobalt on the oxidative status in heart and aorta of streptozotocin-induced diabetic rats. Cell Biochem Funct 21: 27–33
Acknowledgements
We thank Violet G. Yuen and Mary Battell for their assistance through the course of this study. This study was supported by a grant from the Canadian Institutes of Health Research to Dr. McNeill. Harish Vasudevan received financial support from a program grant from the Heart and Stroke Foundation of BC and Yukon.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Vasudevan, H., McNeill, J.H. Chronic Cobalt Treatment Decreases Hyperglycemia in Streptozotocin-Diabetic Rats. Biometals 20, 129–134 (2007). https://doi.org/10.1007/s10534-006-9020-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10534-006-9020-4