Abstract
Vanadium is a well known anti-diabetic agent which mimics most of the actions of insulin on mature adipocytes. We report here the effect of vanadium on proliferation and differentiation of 3T3-L1 preadipocytes. Like insulin, vanadium treatment leads to increased proliferation as evidenced by H3thymidine uptake studies and differentiation of 3T3-L1 cells into adipocytes as evidenced by oil-red-O staining. Adipogenic potential of vanadium can be attributed to CREB activation, as documented by phospho-CREB antibody staining. This adipogenic potential is of significance in an in vivo scenario as the new adipocytes are likely to be insulin sensitive as against resistant existing mature adipocytes and thus indirectly may help in reduction of insulin resistance. Till today decrease in insulin resistance by vanadium treatment has been mainly attributed to its potential to inhibit PTP-1B, however the present study opens a new dimension in vanadium treatment for diabetes due to its novel role in adipogenesis.
Similar content being viewed by others
Abbreviations
- DMEM:
-
Dulbecco’s modified eagle medium
- NBCS:
-
New born calf serum
- CREB:
-
cAMP response element binding protein
- FCS:
-
Fetal calf serum
- FITC:
-
Fluorescein isothiocyanate
References
Beliaeva NF, Gorodetskii VK, Tochilkin AI, Golubev MA, Semenova NV, Kovel’man IR (2000) Vanadium compounds-a new class of therapeutic agents for the treatment of diabetes mellitus. Vopr Med Khim 46:344–360
Boden G, Chen X, Ruiz J, van Rossum GD, Turco S (1996) Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus. Metabolism 45:1130–1135
Dubyak GR, Kleinzeller A (1980) The insulin-mimetic effects of vanadate in isolated rat adipocytes. Dissociation from effects of vanadate as (Na+-K+)ATPase inhibitor. J Biol Chem 255:5306–5312
Fonseca V (2003) Effect of thiazolidinediones on body weight in patients with diabetes mellitus. Am J Med 115(Suppl 8A):42S–48S
Goldfine AB, Patti ME, Zuberi L, Goldstein BJ, LeBlanc R, Landaker EJ, Jiang ZY, Willsky GR, Kahn CR. (2000) Metabolic effects of vanadyl sulfate in humans with non-insulin-dependent diabetes mellitus: in vivo and in vitro studies. Metabolism 49:400–410
Gregoire FM, Smas CM, Sul HS (1998) Understanding adipocyte differentiation. Physiol Rev 78:783–809
Gregoire FM (2001) Adipocyte differentiation: from fibroblast to endocrine cell. Exp Biol Med 226:997–1002
Guller S, Corin RE, Mynarcik DC, London BM, Sonenberg M (1988) Role of insulin in growth hormone-stimulated 3T3 cell adipogenesis. Endocrinology 122:2084–2089
Klemm DJ, Leitner JW, Watson P, Nesterova A, Reusch JE, Goalstone ML, Draznin B. (2001) Insulin-induced adipocyte differentiation. Activation of CREB rescues adipogenesis from the arrest caused by inhibition of prenylation. J Biol Chem 276:28430–28435
Klemm DJ, Roesler WJ, Boras T, Colton LA, Felder K, Reusch JEB (1998) Insulin stimulates cAMP-response element binding protein activity in HepG2 and 3T3-L1 cell lines. J Biol Chem 273:917–923
Mehdi MZ, Pandey SK, Theberge JF, Srivastava AK (2006) Insulin signal mimicry as a mechanism for the insulin-like effects of vanadium. Cell Biochem Biophys 44:73–81
Reusch JE, Colton LA, Klemm DJ (2000) CREB activation induces adipogenesis in 3T3-L1 cells. Mol Cell Biol 20:1008–1020
Shukla R, Barve V, Padhye S, Bhonde R (2004) Synthesis, structural properties and insulin-enhancing potential of bis(quercetinato)oxovanadium(IV) conjugate. Bioorg Med Chem Lett 14:4961–4965
Shukla R, Barve V, Padhye S, Bhonde R. (2006) Reduction of oxidative stress induced vanadium toxicity by complexing with a flavonoid, quercetin: a pragmatic therapeutic approach for diabetes. Biometals 19:685–693
Sinha D, Addya S, Murer E, Boden G (1999) 15-Deoxy-delta(12,14) prostaglandin J2: a putative endogenous promoter of adipogenesis suppresses the ob gene. Metabolism 48:786–791
Smith JB (1983) Vanadium ions stimulate DNA synthesis in Swiss mouse 3T3 and 3T6 cells. Proc Natl Acad Sci 80:6162–6166
Srivastava AK (2000) Anti-diabetic and toxic effects of vanadium compounds. Mol Cell Biochem 206:177–182
Srivastava AK, Mehdi MZ (2005) Insulino-mimetic and anti-diabetic effects of vanadium compounds. Diabet Med 22:2–13
Tafuri SR. (1996) Troglitazone enhances differentiation, basal glucose uptake, and Glut1 protein levels in 3T3-Ll adipocytes. Endocrinology 137:4706–4712
Tchoukalova YD, Hausman DB, Dean RG, Hausman GJ (2000) Enhancing effect of troglitazone on porcine adipocyte differentiation in primary culture: a comparison with dexamethasone. Obes Res 8:664–672
Theberge JF, Mehdi MZ, Pandey SK, Srivastava AK. (2003) Prolongation of insulin-induced activation of mitogen-activated protein kinases ERK 1/2 and phosphatidylinositol 3-kinase by vanadyl sulfate, a protein tyrosine phosphatase inhibitor. Arch Biochem Biophys 420:9–17
Wang J, Yuen VG, McNeill JH. (2001) Effect of vanadium on insulin sensitivity and appetite. Metabolism 50:667–673
Acknowledgement
Authors wish to thank Director, NCCS for providing all the experimental facilities and Council for scientific and industrial research (CSIR), India for research fellowship to RS. Also the authors thank Dr Subhash Padhye for providing VOSO4.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Shukla, R., Bhonde, R.R. Adipogenic action of vanadium: a new dimension in treating diabetes. Biometals 21, 205–210 (2008). https://doi.org/10.1007/s10534-007-9109-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10534-007-9109-4