Biological Trace Element Research

, Volume 131, Issue 2, pp 133–142 | Cite as

Chromium Improves Glucose Uptake and Metabolism Through Upregulating the mRNA Levels of IR, GLUT4, GS, and UCP3 in Skeletal Muscle Cells

  • Wei Qiao
  • Zhongli Peng
  • Zhisheng Wang
  • Jing Wei
  • Anguo ZhouEmail author


The aim of this study was to evaluate the impact of three different chromium forms as chromic chloride (CrCl), chromium picolinate (CrPic), and a newly synthesized complex of chromium chelated with small peptides (CrSP) on glucose uptake and metabolism in vitro. In cultured skeletal muscle cells, chromium augmented insulin-stimulated glucose uptake and metabolism as assessed by a reduced glucose concentration of culture medium. At the molecular level, insulin significantly increased the mRNA levels of insulin receptor (IR), glucose transporter 4 (GLUT4), glycogen synthase (GS), and uncoupling protein-3 (UCP3), and these impacts can be enhanced by the addition of chromium, especially in the form of CrSP. Collectively, results of this study demonstrate that chromium improves glucose uptake and metabolism through upregulating the mRNA levels of IR, GLUT4, GS, and UCP3 in skeletal muscle cells, and CrSP has higher efficacy on glucose uptake and metabolism compared to the forms of CrCl and CrPic.


Chromium Insulin Glucose uptake Glucose metabolism Insulin receptor Glucose transporter 4 Glycogen synthase Uncoupling protein-3 



This article was financially supported by the Program for Changjiang Scholars and Innovative Research Team in University, China, IRTO555.


  1. 1.
    Vincent JB (2001) The biochemistry of chromium. J Nutr 130:715–718Google Scholar
  2. 2.
    Stearns DM, Belbruno JJ, Wetterhahn KE (1995) A prediction of chromium(III) accumulation in humans from chromium dietary supplements. FASEB J 9:1650–1657PubMedGoogle Scholar
  3. 3.
    Speetjens JK, Collins RA, Vincent JB, Woski SA (1999) The nutritional supplement chromium(III) tris(picolinate) cleaves DNA. Chem Res Toxicol 12:483–487PubMedCrossRefGoogle Scholar
  4. 4.
    Anderson RA, Bryden NA, Polansky MM, Gautschi K (1996) Dietary chromium effects on tissue chromium concentrations and chromium absorption in rats. J Trace Elem Exp Med 9:11–17CrossRefGoogle Scholar
  5. 5.
    Yang XP, Palanichamy K, Ontko AC, Rao MNA, Fang CX, Ren J, Sreejayan N (2005) A newly synthetic chromium complex—chromium (phenylalanine)3 improves insulin responsiveness and reduces whole body glucose tolerance. FEBS Lett 579:1458–1464PubMedCrossRefGoogle Scholar
  6. 6.
    Peng ZL, Qiao W, Zhou AG, Wang ZS, Chen ZH (2008) Absorption of different sources of chromium by broiler chicken. Chin J Anim Nutr 20:128–132Google Scholar
  7. 7.
    Yoshimoto S, Sakamoto K, Wakabayashi I, Masui H (1992) Effect of chromium administration on glucose tolerance in stroke-prone spontaneously hypertensive rats with streptozotocin induced diabetes. Metabolism 41:636–642PubMedCrossRefGoogle Scholar
  8. 8.
    Davis CM, Vincent JB (1997) Chromium oligopeptide activates insulin receptor tyrosine kinase activity. Biochemistry 36:4382–4385PubMedCrossRefGoogle Scholar
  9. 9.
    Huppertz C, Fischer BM, Kim YB, Kotani K, Vidal-Puig A, Sliekeri LJ, Sloopi KW, Lowell BB, Kahn BB (2001) Uncoupling protein 3 (UCP3) stimulates glucose uptake in muscle cells through a phosphoinositide 3-kinase-dependent mechanism. J Biol Chem 276:12520–12529PubMedCrossRefGoogle Scholar
  10. 10.
    Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods 25:402–428PubMedCrossRefGoogle Scholar
  11. 11.
    Miranda ER, Dey CS (2004) Effect of chromium and zinc on insulin signaling in skeletal muscle cells. Biol Trace Elem Res 101:19–36PubMedCrossRefGoogle Scholar
  12. 12.
    Shinder UA, Sharma G, Xu YJ, Dhalla NS, Goyal RK (2004) Insulin sensitising action of chromium picolinate in various experimental models of diabetes mellitus. J Trace Elem Med Biol 18:23–32CrossRefGoogle Scholar
  13. 13.
    Anderson RA (1998) Chromium, glucose intolerance and diabetes. J Am Coll Nutr 17:548–555PubMedGoogle Scholar
  14. 14.
    Volek JS, Silvestre RR, Kirwan JP, Sharnan MJ, Judelson DA, Spiering BA, Vingren JL, Maresh CM, Vanheest JL, Kraemer WJ (2006) Effects of chromium supplementation on glycogen synthesis after high-intensity exercise. Med Sci Sports Exerc 38:2102–2109PubMedCrossRefGoogle Scholar
  15. 15.
    Baron AD, Brechtel G, Wallace P, Edelman SV (1988) Rates and tissue sites of non-insulin-and insulin-mediated glucose uptake in humans. Am J Physiol 255:E769–E774PubMedGoogle Scholar
  16. 16.
    DeFronzo RA, Ferrannini E, Sato Y, Felig P, Wahren J (1981) Synergistic interaction between exercise and insulin on peripheral glucose uptake. J Clin Invest 68:1468–1474PubMedCrossRefGoogle Scholar
  17. 17.
    Shulman GI, Rothman DL, Jue T, Stein P, DeFronzo RA, Shulman RG (1990) Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Engl J Med 322:223–228PubMedGoogle Scholar
  18. 18.
    Kraegen EW, James DE, Jenkins AB, Chisholm DJ (1985) Dose–response curves for in vivo insulin sensitivity in individual tissues in rats. Am J Physiol 248:E353–E362PubMedGoogle Scholar
  19. 19.
    Tsao TS, Burcelin R, Katz EB, Huang L, Charron MJ (1996) Enhanced insulin action due to targeted GLUT4 overexpression exclusively in muscle. Diabetes 45:28–36PubMedCrossRefGoogle Scholar
  20. 20.
    Tsao TS, Stenbit AE, Li J, Houseknecht KL, Zierath JR, Katz EB, Charron MJ (1997) Muscle-specific transgenic complementation of GLUT4-deficient mice: effects on glucose but not lipid metabolism. J Clin Invest 100:671–677PubMedCrossRefGoogle Scholar
  21. 21.
    Hansen PA, Gulve EA, Marshall BA, Gao J, Pessin JE, Holloszy JO, Mueckler M (1995) Skeletal muscle glucose transport and metabolism are enhanced in transgenic mice overexpressing the Glut4 glucose transporter. J Biol Chem 270:1679–1684PubMedCrossRefGoogle Scholar
  22. 22.
    Treadway JL, Hargrove DM, Nardone NA, McPherson RK, Russo JF, Milici AJ, Stukenbrok HA, Gibbs EM, Stevenson RW, Pessin JE (1994) Enhanced peripheral glucose utilization in transgenic mice expressing the human GLUT4 gene. J Biol Chem 269:29956–29961PubMedGoogle Scholar
  23. 23.
    Ren JM, Marshall BA, Mueckler MM, McCaleb M, Amatruda JM, Shulman GI (1995) Overexpression of Glut4 protein in muscle increases basal and insulin-stimulated whole body glucose disposal in conscious mice. J Clin Invest 95:429–432PubMedCrossRefGoogle Scholar
  24. 24.
    Deems RO, Evans JL, Deacon RW, Honer CM, Chu DT, Burki K, Fillers WS, Cohen DK, Young DA (1994) Expression of human GLUT4 in mice results in increased insulin action. Diabetologia 37:1097–1104PubMedCrossRefGoogle Scholar
  25. 25.
    Leturque A, Loizeau M, Vaulont S, Salminen M, Girard J (1996) Improvement of insulin action in diabetic transgenic mice selectively overexpressing GLUT4 in skeletal muscle. Diabetes 45:23–27PubMedCrossRefGoogle Scholar
  26. 26.
    Tsao TS, Stenbit AE, Factor SM, Chen W, Rossetti L, Charron MJ (1999) Prevention of insulin resistance and diabetes in mice heterozygous for GLUT4 ablation by transgenic complementation of GLUT4 in skeletal muscle. Diabetes 48:775–782PubMedCrossRefGoogle Scholar
  27. 27.
    Tsao TS, Katz EB, Pommer D, Charron MJ (2000) Amelioration of insulin resistance but not hyperinsulinemia in obese mice overexpressing GLUT4 selectively in skeletal muscle. Metabolism 49:340–346PubMedCrossRefGoogle Scholar
  28. 28.
    Pessin JE, Thurmond DC, Elmendorf JS, Coker KJ, Okada S (1999) Molecular basis of insulin-stimulated GLUT4 vesicle trafficking. Location! Location! Location! J Biol Chem 274:2593–2596PubMedCrossRefGoogle Scholar
  29. 29.
    Satoh S, Nishimura H, Clark AE, Kozka IJ, Vannucci SJ, Simpson IA, Quon MJ, Cushman SW, Holman GD (1993) Use of bismannose photolabel to elucidate insulin-regulated GLUT4 subcellular trafficking kinetics in rat adipose cells. Evidence that exocytosis is a critical site of hormone action. J Biol Chem 268:17820–17829PubMedGoogle Scholar
  30. 30.
    Jhun BH, Rampal AL, Liu H, Lachaal M, Jung CY (1992) Effects of insulin on steady state kinetics of GLUT4 subcellular distribution in rat adipocytes. Evidence of constitutive GLUT4 recycling. J Biol Chem 267:17710–17715PubMedGoogle Scholar
  31. 31.
    Czech MP, Buxton JM (1993) Insulin action on the internalization of the GLUT4 glucose transporter in isolated rat adipocytes. J Biol Chem 268:9187–9190PubMedGoogle Scholar
  32. 32.
    Bouskila M, Hirshman MF, Jensen J, Goodyear LJ, Sakamoto K (2008) Insulin promotes glycogen synthesis in the absence of GSK3 phosphorylation in skeletal muscle. Am J Physiol Endocrinol Metab 294:E28–E35PubMedCrossRefGoogle Scholar
  33. 33.
    Wang ZQ, Zhang XH, Cefalu WT (2000) Chromium picolinate and biotin enhance glycogen synthesis and glycogen synthase gene expression in human skeletal muscle culture. Diabetes Res Clin Pract 50 Supp 1:395CrossRefGoogle Scholar
  34. 34.
    Krook ADJ, O’Rahilly S, Zierath JR, Wallberg-Henriksson H (1998) Uncoupling protein 3 is reduced in skeletal muscle of NIDDM patients. Diabetes 47:1528–1531PubMedCrossRefGoogle Scholar
  35. 35.
    Vidal-Puig AJ, Grujic D, Zhang CY, Hagen T, Boss O, Ido Y, Szczepanik A, Wade J, Mootha V, Cortright R, Muoio DM, Lowell BB (2000) Energy metabolism in uncoupling protein 3 gene knockout mice. J Biol Chem 275:16258–16266PubMedCrossRefGoogle Scholar
  36. 36.
    Gong DW, Monemdjou S, Gavrilova O, Leon LR, Marcus-Samuels B, Chou CJ, Everett C, Kozak LP, Li C, Deng C, Harper ME, Reitman ML (2000) Lack of obesity and normal response to fasting and thyroid hormone in mice lacking uncoupling protein-3. J Biol Chem 275:16251–16257PubMedCrossRefGoogle Scholar
  37. 37.
    Clapham JC, Arch JR, Chapman H, Haynes A, Lister C, Moore GB, Piercy V, Carter SA, Lehner I, Smith SA, Beeley LJ, Godden RJ, Herrity N, Skehel M, Changani KK, Hockings PD, Reid DG, Squires SM, Hatcher J, Trail B, Latcham J, Rastan S, Harper AJ, Cadenas S, Buckingham JA, Brand MD, Abuin A (2000) Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean. Nature 406:415–418PubMedCrossRefGoogle Scholar
  38. 38.
    Li B, Nolte LA, Ju JS, Ho Han D, Coleman T, Holloszy JO, Semenkovich CF (2000) Skeletal muscle respiratory uncoupling prevents diet-induced obesity and insulin resistance in mice. Nat Med 6:1115–1120PubMedCrossRefGoogle Scholar
  39. 39.
    Chen NS, Tsai CA, Dyer IA (1973) Effect of chelating agents on chromium absorption in rats. J Nutr 103:1182–1186PubMedGoogle Scholar
  40. 40.
    Sun Y, Ramirez J, Woski SA, Vincent JB(2000)The binding of trivalent chromium to low-molecular-weight chromium-binding substance (LMWCr) and the transfer of chromium from transferrin and chromium picolinate to LMWCr. JBIC 5:129–136PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2009

Authors and Affiliations

  • Wei Qiao
    • 1
  • Zhongli Peng
    • 2
  • Zhisheng Wang
    • 1
  • Jing Wei
    • 3
  • Anguo Zhou
    • 1
    Email author
  1. 1.Engineering Research Center of Animal Disease-Resistance Nutrition of ChinaMinistry of EducationYa’anChina
  2. 2.Southwest University for NationalitiesChengduChina
  3. 3.The second Station for Feed Quality Monitoring and Inspection of Sichuan ProvinceChengduChina

Personalised recommendations