Abstract
Vanadium exhibits a variety of insulin-mimetic actions in vitro and in vivo. The mechanism(s) of the effect of vanadium on leptin in Zucker diabetic fatty (ZDF) rats, a model of Type 2 diabetes, is unclear. Since insulin is a stimulator of leptin production and secretion and vanadium is an insulin-mimetic or insulin-enhancing agent, we studied how vanadium affected plasma leptin levels in vivo and the relationship between plasma insulin, leptin and body fat in ZDF rats. Zucker lean and ZDF rats at 9-week old were chronically treated with bis(ethylmaltolato)oxovanadium(IV) (BEOV), an organic vanadium compound, by oral gavage daily for 3 weeks. At termination, the total body fat was weighed and blood was collected for insulin, leptin and glucose assay. BEOV treatment (0.1 mmol/kg/day) significantly decreased plasma glucose levels in ZDF rats and did not change food intake and body fat content either in lean or ZDF rats. Following 3-week treatment, plasma insulin and leptin levels in BEOV treated ZDF rats were significantly higher, 1.5 and 0.5 fold than untreated rats, respectively. The correlation coefficients in ZDF rats showed that plasma leptin levels were correlated to plasma insulin levels, but not to body fat. These data indicate that plasma leptin levels parallel plasma insulin levels, and the effects of vanadium on leptin appear to be mediated by insulin in ZDF rats.
Similar content being viewed by others
References
Duckworth WC, Solomon SS, Liepnieks J, Hamel FG, Hand S, Peavy DE: Insulin-like effects of vanadate in isolated rat adipocytes. Endocrinology 122: 2285–2289, 1988
Shechter Y, Karlish SJ: Insulin-like stimulation of glucose oxidation in rat adipocytes by vanadyl (IV) ions. Nature 284: 556–558, 1980
Tsiani E, Abdullah N, Fantus IG: Insulin-mimetic agents vanadate and pervanadate stimulate glucose but inhibit amino acid uptake. Am J Physiol 272: C156–C162, 1997
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. Can J Physiol Pharmacol 73: 55–64, 1995
Yuen VG, Vera E, Battell ML, Li WM, McNeill JH: Acute and chronic oral administration bis(maltolato)oxovanadium(IV) in Zucker diabetic fatty (ZDF) rats. Diab Res Clin Prac 43: 9–19, 1999
Yuen VG, Pederson RA, Dai S, Orvig C, McNeill JH: Effects of low and high dose administration of bis(maltolato)oxovanadium(IV) on fa/fa Zucker rats. Can J Physiol Pharmacol 74: 1001–1009, 1996
Wang J, Yuen VG, McNeill JH: Effect of vanadium on insulin sensitivity and appetite. Metabolism (in press)
Zhang Y, Proenca R, Maffie M, Barone M, Leopold L, Friedman JM: Positional cloning of the mouse obese gene and its human homologue. Nature 372: 425–432, 1994
Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P: Recombinant mouse OB protein: Evidence for a peripheral signal linking adiposity and central neural networks. Science 269: 546–549, 1995
Pelleymounter MA, Cullen M, Baker MJ, Hecht R, Winters D, Boone T, Collins F: Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269: 540–543, 1995
Considine RV, Considine EL, Williams CJ, Nyce MR, Magosin SA, Bauer TL, Rosato EL, Colberg J, Caro JE: Evidence against either a premature stop codon or the absence of obese gene mRNA in human obesity. J Clin Invest 95: 2986–2988, 1995
Maffer M, Fei H, Lee GH, Dani C, Leroy P, Zhang Y. Proenca R, Negrel R, Aihaud G, Fridman JM: Increased expression in adipocytes of ob RNA in mice with lesions of the hypothalamus and with mutations at the db locus. Proc Natl Acad Sci USA 92: 6957–6960, 1995
Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF: Serum immunoreactive-leptin concentrations in normal weight and obese humans. N Engl J Med 334: 292–295, 1996
Ahern B: Plasma leptin and insulin in C57B1/6J mice on a high fat diet: Relation to subsequent changes in body weight. Acta Physiol Scand 165: 233–240, 1999
Guven S, El-Bershawi A, Sonnenberg GE, Wilson CR, Hoffmann RG, Krakower GR, Kissebah AH: Plasma leptin and insulin levels in weightreduced obese women with normal body mass index. Diabetes 48: 347-352, 1999
Zheng D, Jones JP, Usala SJ, Dohm GL: Differential expression of ob mRNA in rat adipose tissues in response to insulin. Biochem Biophys Res Commun 218: 434–437, 1996
Barr VA, Malide D, Zarnowski MJ, Taylor SI, Cushman SW: Insulin stimulates both leptin secretion and production by rat adipose tissue. Endocrinology 138: 4463–4472, 1997
Janssen SW, Martens GJ, Sweep CG, Ross HA, Hermus AR: In Zucker diabetic fatty rats plasma leptin levels are correlated with plasma insulin levels rather than with body weight. Horm Metab Res 31: 610-615, 1999
Segal KR, Landt M, Klein S: Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men. Diabetes 45: 988–991, 1996
Widjaja A, Stratton IM, Horn R, Holman RR, Turner R, Brabant G: UKPDS 20: Plasma leptin, obesity, and plasma insulin in Type 2 diabetic subjects. J Clin Endocrinol 82: 654–657, 1997
Clark JB, Palmer CJ, Shaw WN: The diabetic Zucker fatty rat. Proc Soc Exp Biol Med 173: 68–75, 1983
Pederson RA, Ramanadham S, Buchan AM, McNeill JH: Long-term effects of vanadyl treatment of streptozocin-induced diabetes in rats. Diabetes 38: 1390–1395, 1989
Dai S, Thompson KH, McNeill JH: One-year treatment of streptozotocin-induced diabetic rats with vanadyl sulphate. Pharmacol Toxicol 74: 101-109, 1994
Cam MC, Li WM, McNeill JH: Partial preservation of pancreatic bcells by vanadium: Evidence for long-term amelioration of diabetes. Metabolism 46: 769–778, 1997
Hickey MS, Considine RV, Israel RG, Mahar TL, McCammon MR, Tyndall GL, Houmard JA, Caro JF: Leptin is related to body fat content in male distance runners. Am J Physiol 271: E938–E940, 1996
Takahashi M, Funahashi T, Shimomura I, Miyaoka K, Matsuzawa Y: Plasma leptin levels and body fat distribution. Horm Metab Res 28: 751–752, 1996
Kolaczynski JW, Nyce MR, Considine RV, Boden G, Nolan JJ, Henry R, Mudaliar SR, Olefsky J, Caro JF: Acute and chronic effects of insulin on leptin production in humans. Studies in vivo and in vitro. Diabetes 45: 699–701, 1996
Saladin R, De Vos P, Guerre-Millo M, Leturque A, Girard J, Staels B, Auwerx J: Transient increase in obese gene expression after food intake or insulin administration. Nature 377: 527–529, 1995
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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). https://doi.org/10.1023/A:1007229910582
Issue Date:
DOI: https://doi.org/10.1023/A:1007229910582