Biological Trace Element Research

, Volume 180, Issue 2, pp 223–232 | Cite as

Effect of Peroral Administration of Chromium on Insulin Signaling Pathway in Skeletal Muscle Tissue of Holstein Calves

  • Ljubomir Jovanović
  • Marija Pantelić
  • Radiša Prodanović
  • Ivan Vujanac
  • Miloje Đurić
  • Snežana Tepavčević
  • Sanja Vranješ-Đurić
  • Goran Korićanac
  • Danijela KirovskiEmail author


The objective of this study was to investigate the effects of peroral administration of chromium-enriched yeast on glucose tolerance in Holstein calves, assessed by insulin signaling pathway molecule determination and intravenous glucose tolerance test (IVGTT). Twenty-four Holstein calves, aged 1 month, were chosen for the study and divided into two groups: the PoCr group (n = 12) that perorally received 0.04 mg of Cr/kg of body mass daily, for 70 days, and the NCr group (n = 12) that received no chromium supplementation. Skeletal tissue samples from each calf were obtained on day 0 and day 70 of the experiment. Chromium supplementation increased protein content of the insulin β-subunit receptor, phosphorylation of insulin receptor substrate 1 at Tyrosine 632, phosphorylation of Akt at Serine 473, glucose transporter-4, and AMP-activated protein kinase in skeletal muscle tissue, while phosphorylation of insulin receptor substrate 1 at Serine 307 was not affected by chromium treatment. Results obtained during IVGTT, which was conducted on days 0, 30, 50, and 70, suggested an increased insulin sensitivity and, consequently, a better utilization of glucose in the PoCr group. Lower basal concentrations of glucose and insulin in the PoCr group on days 30 and 70 were also obtained. Our results indicate that chromium supplementation improves glucose utilization in calves by enhancing insulin intracellular signaling in the skeletal muscle tissue.


Calves Chromium Insulin Signaling pathway AMP-activated protein kinase 



This work was supported by the Ministry of Education, Science and Technological Development, Republic of Serbia (project numbers: III 46002; III 41009; III 41029).

Compliance with Ethical Standards

The animal-related component of the study was approved by the Ethical Committee of the Faculty of Veterinary Medicine, University of Belgrade, in accordance with the National Regulations on Animal Welfare approval no. 323-07-07812/2014-05/3.

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Jeejeebhoy KN, Chu RC, Marliss EB, Greenberg GR, Bruce-Robertson A (1977) Chromium deficiency, glucose intolerance, and neuropathy reversed by chromium supplementation in a patient. Am J Clin Nutr 30:531–538PubMedGoogle Scholar
  2. 2.
    Leiva T, Cooke RF, Aboin AC, Drago FL, Gennari R, Vasconcelos JLM (2014) Effects of excessive energy intake and supplementation with chromium propionate on insulin resistance parameters in nonlactating dairy cows. J Anim Sci 92:775–782CrossRefPubMedGoogle Scholar
  3. 3.
    Deka RS, Mani V, Kumar M, Shiwajirao ZS, Tyagi AK, Kaur H (2014) Body condition, energy balance and immune status of periparturient Murrah buffaloes (Bubalus bubalis) supplemented with inorganic chromium. Biol Trace Elem Res 161:57–68CrossRefPubMedGoogle Scholar
  4. 4.
    Deka SR, Mani V, Kumar M, Shiwajirao ZS, Kaur H (2015) Chromium supplements in the feed for lactating Murrah buffaloes (Bubalus bubalis): influence on nutrient utilization, lactation performance, and metabolic responses. Biol Trace Elem Res 168:362–371CrossRefPubMedGoogle Scholar
  5. 5.
    Liu L, Wang B, He Y, Tao W, Liu Z, Wang M (2016) Effects of chromium-loaded chitosan nanoparticles on glucose transporter 4, relevant mRNA, and proteins of phosphatidylinositol 3-kinase, Akt2-kinase, and AMP-activated protein kinase of skeletal muscles in finishing pigs. Biol Trace Elem Res 174:1–8CrossRefGoogle Scholar
  6. 6.
    Pechova A, Pavlata L (2007) Chromium as an essential nutrient: a review. Vet Med-Czech 52:1–18Google Scholar
  7. 7.
    Rao SV, Prakash B, Raju MV, Panda AK, Kumari RK, Reddy EP (2016) Effect of supplementing organic forms of zinc, selenium and chromium on performance, anti-oxidant and immune responses in broiler chicken reared in tropical summer. Biol Trace Elem Res 172:511–520CrossRefPubMedGoogle Scholar
  8. 8.
    Al-Saiadya MY, Al-Shaikhb MA, Al-Mufarreja SI, Al-Showeimia TA, Mogawera HH, Dirrara A (2004) Effect of chelated chromium supplementation on lactation performance and blood parameters of Holstein cows under heat stress. Anim Feed Sci Tech 117:223–233CrossRefGoogle Scholar
  9. 9.
    Bunting LD, Fernandez JM, Thompson DL, Southern LL (1994) Influence of chromium picolinate on glucose usage and metabolic criteria in growing Holstein calves. J Dairy Sci 72:1591–1599Google Scholar
  10. 10.
    Ghorbani A, Sadri H, Alizadeh AR, Bruckmaier RM (2012) Performance and metabolic response of Holstein calves to supplemental chromium in colostrum and milk. J Dairy Sci 95:5760–5769CrossRefPubMedGoogle Scholar
  11. 11.
    Yari M, Nikkhah A, Alikhani M, Khorvash M, Rahmani H, Ghorbani GR (2010) Physiological calf responses to increased chromium supply in summer. J Dairy Sci 93:4111–4412CrossRefPubMedGoogle Scholar
  12. 12.
    Wang ZQ, Zhang XH, Russell JC, Hulver M, Cefalu WT (2006) Chromium picolinate enhances skeletal muscle cellular insulin signaling in vivo in obese, insulin resistant JCR:LA-cp rats. J Nutr 136:415–420PubMedGoogle Scholar
  13. 13.
    Dong F, Kandadi MR, Ren J, Sreejayan N (2008) Chromium (D-phenylalanine)3 supplementation alters glucose disposal, insulin signaling, and glucose transporter-4 membrane translocation in insulin-resistant mice. J Nutr 138:1846–1851PubMedGoogle Scholar
  14. 14.
    Sreejayan N, Dong F, Kandadi MR, Yang X, Ren J (2008) Chromium alleviates glucose intolerance, insulin resistance, and hepatic ER stress in obese mice. Obesity (Silver Spring) 16:1331–1337CrossRefGoogle Scholar
  15. 15.
    Wang H, Kruszewski A, Brautigan DL (2005) Cellular chromium enhances activation of insulin receptor kinase. Biochemistry 44:8167–8175CrossRefPubMedGoogle Scholar
  16. 16.
    Saltiel AR, Kahn CR (2001) Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414:799–806CrossRefPubMedGoogle Scholar
  17. 17.
    Myers MG Jr, White MF (1993) The new elements of insulin signaling. Insulin receptor substrate-1 and proteins with SH2 domains. Diabetes 42:643–650CrossRefPubMedGoogle Scholar
  18. 18.
    Aguirre V, Werner ED, Giraud J, Lee YH, Shoelson SE, White MF (2002) Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with insulin receptor and inhibits insulin action. J Biol Chem 277:1531–1537CrossRefPubMedGoogle Scholar
  19. 19.
    Hua Y, Clark S, Ren J, Sreejayan N (2012) Molecular mechanisms of chromium in alleviating insulin resistance. J Nutri Bioch 23:313–319CrossRefGoogle Scholar
  20. 20.
    Al-Trad B, Reisberg K, Wittek T, Penner GB, Alkaassem A, Gäbel G, Fürll M, Aschenbach JR (2009) Increasing intravenous infusions of glucose improve body condition but not lactation performance in midlactation dairy cows. J Dairy Sci 92:5645–5658CrossRefPubMedGoogle Scholar
  21. 21.
    Holtenius K, Agenäs S, Delavaud C, Chilliard Y (2003) Effects of feeding intensity during the dry period, metabolic and hormonal responses. J Dairy Sci 86:883–891CrossRefPubMedGoogle Scholar
  22. 22.
    Holtenius P, Holtenius K (2007) A model to estimate insulin sensitivity in dairy cows. Acta Vet Scand 49:29CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Ebara F, Inada S, Morikawa M, Asaoka SH, Isozaki Y, Saito A, Etoh T, Shiotsuka Y, Wegner J, Gotoh T (2013) Effect of nutrient intake on intramuscular glucose metabolism during the early growth stage in cross-bred steers (Japanese Black male · Holstein female). J Anim Physiol An N 97:684–693CrossRefGoogle Scholar
  24. 24.
    Chen WY, Chen CJ, Liu CH, Mao FC (2009) Chromium supplementation enhances insulin signalling in skeletal muscle of obese KK/HlJ diabetic mice. Diabetes Obes Metab 11:293–303CrossRefPubMedGoogle Scholar
  25. 25.
    Gual P, Le Marchand-Brustel Y, Tanti JF (2005) Positive and negative regulation of insulin signaling through IRS-1 phosphorylation. Biochemie 87:99–109CrossRefGoogle Scholar
  26. 26.
    Yang X, Li SY, Dong F, Ren J, Sreejayan N (2006) Insulin-sensitizing and cholesterol-lowering effects of chromium (D-phenylalanine). J Inorg Biochem 100:1187–1193CrossRefPubMedGoogle Scholar
  27. 27.
    Abe H, Kawakita Y, Hodate K, Saito M (2001) Postnatal development of glucose transporter protein in bovine skeletal muscle and adipose tissue. J Vet Med Sci 63:1071–1075CrossRefPubMedGoogle Scholar
  28. 28.
    Castello A, Rodriguez-Manzaneque JC, Camps M, Perez-Castillo A, Testar X, Palacin M, Santos A, Zorzano A (1994) Perinatal hypothyroidism impairs the normal transition of GLUT4 and GLUT1 glucose transporters from fetal to neonatal levels in heart and brown adipose tissue. Evidence for tissue-specific regulation of GLUT4 expression by thyroid hormone. J Bio Chem 269:5905–5912Google Scholar
  29. 29.
    Leng RA (1970) Fermentation and production of volatile fatty acid in the rumen. In: Philipson AT (ed) Physiology of digestation and metabolism in the ruminant. Oriel Press Ltd., Newcastle upon Tyne, pp 406–421Google Scholar
  30. 30.
    Qiao W, Peng Z, Wang Z, Wei J, Zhou A (2009) Chromium improves glucose uptake and metabolism through upregulating the mRNA levels of IR, GLUT4, GS, and UCP3 in skeletal muscle cells. Biol Trace Elem Res 131:133–142CrossRefPubMedGoogle Scholar
  31. 31.
    Zhao P, Wang J, Ma H, Xiao Y, He L, Tong C, Wang Z, Zheng Q, Dolence EK, Nair S, Ren J, Li J (2009) A newly synthetic chromium complex-chromium (D-phenylalanine)3 activates AMP-activated protein kinase and stimulates glucose transport. Biochem Pharmacol 77:1002–1010CrossRefPubMedGoogle Scholar
  32. 32.
    Penumathsa SV, Thirunavukkarasu M, Samuel SM, Zhan L, Maulik G, Bagchi M, Bagchi D, Maulik N (2009) Niacin bound chromium treatment induces myocardial Glut-4 translocation and caveolar interaction via Akt, AMPK and eNOS phosphorylation in streptozotocin induced diabetic rats after ischemia-reperfusion injury. Biochim Biophys Acta 1792:39–48CrossRefPubMedGoogle Scholar
  33. 33.
    Richter EA, Hargreaves M (2013) Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev 93:993–1017CrossRefPubMedGoogle Scholar
  34. 34.
    Matsubara A, Takahashi H, Saito A, Nomura A, Sithyphone K, Mcmahon CD, Fujino R, Shiotsuka Y, Etoh T, Furuse M, Gotoh T (2015) Effects of a high milk intake during the pre-weaning period on nutrient metabolism and growth rate in Japanese black cattle. Anim Sci J 86:1–7CrossRefGoogle Scholar
  35. 35.
    Hocquette FL (2010) Endocrine and metabolic regulation of muscle growth and body composition in cattle. Animal 4:1797–1809CrossRefPubMedGoogle Scholar
  36. 36.
    Horvath EM, Tackett L, McCarthy AM, Raman P, Brozinick JT, Elmendorf JS (2008) Antidiabetogenic effects of chromium mitigate hyperinsulinemia-induced cellular insulin resistance via correction of plasma membrane cholesterol imbalance. Mol Endocrinol 22:937–950CrossRefPubMedGoogle Scholar
  37. 37.
    Kamiya M, Matsuzaki M, Orito H, Kamiya Y, Nakamura YN, Tsuneishi E (2009) Effects of feeding level of milk replacer on body growth, plasma metabolite and insulin concentrations, and visceral organ growth of suckling calves. Anim Sci J 80:662–668CrossRefPubMedGoogle Scholar
  38. 38.
    Maccari P, Wiedemann S, Kunz HJ, Piechotta M, Sanftleben P, Kaske M (2015) Effects of two different rearing protocols for Holstein bull calves in the first 3 weeks of life on health status, metabolism and subsequent performance. J Anim Physiol An N 99:737–746CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Ljubomir Jovanović
    • 1
  • Marija Pantelić
    • 2
  • Radiša Prodanović
    • 3
  • Ivan Vujanac
    • 3
  • Miloje Đurić
    • 4
  • Snežana Tepavčević
    • 2
  • Sanja Vranješ-Đurić
    • 5
  • Goran Korićanac
    • 2
  • Danijela Kirovski
    • 1
    Email author
  1. 1.Department for Physiology and Biochemistry, Faculty of Veterinary MedicineUniversity of BelgradeBelgradeSerbia
  2. 2.Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear SciencesUniversity of BelgradeBelgradeSerbia
  3. 3.Department for Ruminants and Swine Diseases, Faculty of Veterinary MedicineUniversity of BelgradeBelgradeSerbia
  4. 4.Department for Reproduction, Fertility and Artificial Insemination, Faculty of Veterinary MedicineUniversity of BelgradeBelgradeSerbia
  5. 5.Laboratory for Radioisotopes, Vinča Institute of Nuclear SciencesUniversity of BelgradeBelgradeSerbia

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