Molecular and Cellular Biochemistry

, Volume 360, Issue 1–2, pp 401–409 | Cite as

Natural vanadium-containing Jeju ground water stimulates glucose uptake through the activation of AMP-activated protein kinase in L6 myotubes

  • Seung-Lark Hwang
  • Hyeun Wook Chang


The aim of this study was to elucidate the effects of natural vanadium-containing Jeju ground water on glucose uptake in L6 myotubes and adipogensesis in 3T3 L1 cells. The Jeju ground water samples containing vanadium components were designated as S1 (8.0 ± 0.9 μg/l), S2 (24.0 ± 2.0 μg/l), and S3 (26.0 ± 2.0 μg/l), respectively. To investigate the effects of the Jeju ground water on glucose uptake in L6 myotubes, L6 cells were differentiated in media containing deionized distilled water (DDW group) and the water samples (S1, S2, and S3 groups). After daily changes in cultured media containing the Jeju ground water samples for 1 week, all samples had increased glucose uptake compared to the DDW group and the order of glucose uptake increased in parallel with vanadium content (S3 > S2 > S1). In addition, S3 significantly stimulated the phosphorylation of the Thr-172 residue of the AMP-activated protein kinase-α subunit and the Ser-79 subunit of acetyl-CoA carboxylase compared to the DDW group. The effect of glucose uptake by S3 was reversed by pretreatment with Compound C, an AMPK inhibitor. Interestingly, vanadium pentoxide also increased glucose uptake and activated AMPK activity in a dose-dependent manner. Furthermore, as compared to the DDW treated group, S3 treatment inhibited adipogenesis of 3T3-L1 cells by down regulation of expressions of adipogenic transcription factors. Taken together, these findings suggest that S3 displays beneficial effects in the treatment of diabetes, at least in part through the activation of AMPK activity.


Vanadium-containing Jeju ground water AMP-activated protein kinase Glucose uptake Type 2 diabetes Vanadium pentoxide Adipogenesis 



This research was financially supported by the Ministry of Knowledge Economy (MKE), Korea Institute for Advancement of Technology (KIAT) and Jeju Leading Industry Office through the Leading Industry Development for Economic Region and by 2010 Yeungnam University Research Grant.


  1. 1.
    DeFronzo RA (1988) The triumvirate: β-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37:667–687PubMedGoogle Scholar
  2. 2.
    DeFronzo RA, Simonson D, Ferrannini E (1982) Hepatic and peripheral insulin resistance: a common feature of type 2 (non-insulin-dependent) and type 1 (insulin-dependent) diabetes mellitus. Diabetologia 23:313–319PubMedCrossRefGoogle Scholar
  3. 3.
    Heyliger CE, Tahiliani AG, McNeill JH (1985) Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science 227:1474–1477PubMedCrossRefGoogle Scholar
  4. 4.
    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 45:1130–1135PubMedCrossRefGoogle Scholar
  5. 5.
    Hardie DG, Scott JW, Pan DA, Hudson ER (2003) Management of cellular energy by the AMP-activated protein kinase system. FEBS Lett 546:113–120PubMedCrossRefGoogle Scholar
  6. 6.
    Carling D (2004) The AMP-activated protein kinase cascade-a unifying system for energy control. Trends Biochem Sci 29:18–24PubMedCrossRefGoogle Scholar
  7. 7.
    Kurth-Kraczek EJ, Hirshman MF, Goodyear LJ, Winder WW (1999) 5-AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. Diabetes 48:1667–1671PubMedCrossRefGoogle Scholar
  8. 8.
    Hardie DG, Hawley SA (2001) AMP-activated protein kinase: the energy charge hypothesis revisited. Bioassays 23:1112–1119CrossRefGoogle Scholar
  9. 9.
    Russell RR, Bergeron R, Shulman GI, Young LH (1999) Translocation of myocardial GLU-T4 ad increased glucose uptake through activation of AMPK by AICAR. Am J Physiol 277:H643–H649PubMedGoogle Scholar
  10. 10.
    Shulman GI (1987) Cellular mechanisms of insulin resistance. J Clin Invest 106:171–176CrossRefGoogle Scholar
  11. 11.
    Merrill GF, Kurth EJ, Hardie DG, Winder WW (1997) AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am J Physiol 273:E1107–E1112PubMedGoogle Scholar
  12. 12.
    Aschenbach WG, Sakamoto K, Goodyear LJ (2004) 5′ Adenosine monophosphate-activated protein kinase, metabolism and exercise. Sports Med 34:91–103PubMedCrossRefGoogle Scholar
  13. 13.
    Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ, Shulman GI (2002) AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci USA 99:15983–15987PubMedCrossRefGoogle Scholar
  14. 14.
    Mu J, Brozinick JT Jr, Valladares O, Bucan M, Birnbaum MJ (2001) A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle. Mol Cell 7:1085–1094PubMedCrossRefGoogle Scholar
  15. 15.
    Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108:1167–1174PubMedGoogle Scholar
  16. 16.
    Fryer LG, Parbu-Patel A, Carling D (2002) The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J Biol Chem 277:25226–25232PubMedCrossRefGoogle Scholar
  17. 17.
    Mandrup S, Lane MD (1997) Regulating adipogenesis. J Biol Chem 272:5367–5370PubMedCrossRefGoogle Scholar
  18. 18.
    Hwang SL, Yang BK, Lee JY, Kim JH, Kim BH, Suh KH, Kim DY, Kim MS, Song H, Park BS, Huh TL (2008) Isodihydrocapsiate stimulates plasma glucose uptake by activation of AMP-activated protein kinase. Biochem Biophys Res Commun 371:289–293PubMedCrossRefGoogle Scholar
  19. 19.
    Zhou G, Myers R, Chen Y, Shen X (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108:1167–1174PubMedGoogle Scholar
  20. 20.
    Shechter Y (1990) Insulin-mimetic effects of vanadate. Possible implications for future treatment of diabetes. Diabetes 39:1–5PubMedCrossRefGoogle Scholar
  21. 21.
    Domingo JL, Gomez M, Sanchez DJ, Llobet JM, Keen CL (1995) Toxicology of vanadium compounds in diabetic rats: the action of chelating agents on vanadium accumulation. Mol Cell Biochem 153:233–240PubMedCrossRefGoogle Scholar
  22. 22.
    Srivastava AK, Mehdi MZ (2005) Insulino-mimetic and anti-diabetic effects of vanadium compounds. Diabet Med 22:2–13PubMedCrossRefGoogle Scholar
  23. 23.
    Hadie DG, Carling D (1997) The AMP-activated protein kinase-fuel gauge of the mammalial cell? Eur J Biochem 246:259–273CrossRefGoogle Scholar
  24. 24.
    Hayashi T, Hirshman MF, Fujii N, Habinowski SA, Witters LA, Goodyear LJ (2000) Metabolic stress and altered glucose transport: activation of AMP-activated protein kinase as a unifying coupling mechanism. Diabetes 49:527–531PubMedCrossRefGoogle Scholar
  25. 25.
    Kemp BE, Mitchelhill KI, Stapleton D, Michell BJ, Chen ZP, Witters LA (1999) Dealing with energy demand: the AMP-activated protein kinase. Trends Biochem Sci 24:22–25PubMedCrossRefGoogle Scholar
  26. 26.
    Hayashi T, Hirshman MF, Kurth EJ, Winder WW, Goodyear LJ (1998) Evidence for 5′-AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes 47:1369–1373PubMedCrossRefGoogle Scholar
  27. 27.
    Bergeron R, Russell RR, Young LH, Ren JM, Marcucci M, Lee A, Shulman GI (1999) Effect of AMPK activation on muscle glucose metabolism in conscious rats. Am J Physiol 276:E938–E944PubMedGoogle Scholar
  28. 28.
    Sullivan JE, Brocklehurst KJ, Marley AE, Carey F, Carling D, Beri RK (1994) Inhibition of lipolysis and lipogenesis in isolated rat adipocytes with AICAR, a cell permeable activator of AMP-activated protein kinase. FEBS Lett 353:33–36PubMedCrossRefGoogle Scholar
  29. 29.
    Bergeron R, Previs SF, Cline GW, Perret P, Russell RR III, Young LH, Shulman GI (2001) Effect of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats. Diabetes 50:1076–1082PubMedCrossRefGoogle Scholar
  30. 30.
    Yin W, Mu J, Birnbaum MJ (2003) Role of AMP-activated protein kinase in cyclic AMP-dependent lipolysis in 3T3–L1 adipocytes. J Biol Chem 278:43074–43080PubMedCrossRefGoogle Scholar
  31. 31.
    Hawley SA, Pan DA, Mustard KJ, Ross L, Bain J, Edelman AM, Frenguelli BG, Hardie DG (2005) Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab 2:9–19PubMedCrossRefGoogle Scholar
  32. 32.
    Hurley RL, Anderson KA, Franzone JM, Kemp BE, Means AR, Witters LA (2005) The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J Biol Chem 280:29060–29066PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  1. 1.College of PhamacyYeungnam UniversityGyeongsanRepublic of Korea

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