Download PDF
Horm Metab Res 2014; 46(02): 109-115
DOI: 10.1055/s-0033-1354401
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Expression and Cellular Distribution of Glucose Transporters and Alpha Subunits of Na+/K+-ATPase in the Heart of Fructose-fed Female Rats: The Role of Estradiol

G. Koricanac
1   Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia
,
S. Tepavcevic
1   Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia
,
S. Romic
1   Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia
,
T. Milosavljevic
1   Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia
,
M. Stojiljkovic
1   Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia
,
Z. Zakula
1   Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia
› Author Affiliations
Further Information

Publication History

received 17 April 2013

accepted 12 August 2013

Publication Date:
16 September 2013 (online)

Also available at
    Permissions and Reprints

Abstract

Remarkable parallels are observed between glucose transporters (GLUT) and subunits of Na+/K+-ATPase, which deal with insulin regulation, tissue specificity, intracellular distribution and function of these proteins. To test our hypothesis that similarities also exist in alteration of cardiac GLUTs and alpha subunit isoforms of the pump in insulin resistance, animal model of fructose rich diet was exploited. The role of estradiol in regulation of GLUTs and Na+/K+-ATPase in insulin resistance context was studied as well. Cardiac protein expression, as well as insulin-regulated cellular localization of GLUT4, GLUT1, and α1 and α2 subunits of the pump were analyzed by Western blot. Fructose rich diet increased plasma insulin level and HOMA index, while estradiol treatment reversed both parameters to the control level. We did not observe obvious similarities in the pattern of alterations of GLUT1/α1 subunit of the pump, as well as GLUT4/α2 subunit, related to diet or hormone treatment. Considering alterations in expression and cellular localization of GLUTs and the pump subunits, fructose rich diet jeopardized cardiac glucose transport in some extent, but in contrast, stimulated Na+/K+-ATPase function. Estradiol treatment opposed the fructose diet biochemical action and the effect on cardiac GLUTs, but was inefficient concerning the changes of cardiac Na+/K+-ATPase subunits. Changes of the cardiac molecules can be mediated by alterations in the level of insulin and nonesterified fatty acids, induced by the diet and hormone treatment.

Key words

fructose - estradiol - glucose transporter - sodium-potassium-­exchanging ATPase - heart
 

  • References

  • 1 Kodde IF, van der Stok J, Smolenski RT, de Jong JW. Metabolic and genetic regulation of cardiac energy substrate preference. Comparative Biochemistry and Physiology Part A, Molecular and Integrative Physiology 2007; 146: 26-39
    CrossrefPubMedGoogle Scholar
  • 2 Glatz JF, Bonen A, Ouwens DM, Luiken JJ. Regulation of sarcolemmal transport of substrates in the healthy and diseased heart. Cardiovasc Drugs Ther 2006; 20: 471-476
    CrossrefPubMedGoogle Scholar
  • 3 Bers DM, Barry WH, Despa S. Intracellular Na+ regulation in cardiac myocytes. Cardiovasc Res 2003; 57: 897-912
    CrossrefPubMedGoogle Scholar
  • 4 Sweeney G, Klip A. Regulation of the Na+/K+-ATPase by insulin: why and how?. Mol Cell Biochem 1998; 182: 121-133
    CrossrefPubMedGoogle Scholar
  • 5 Zakula Z, Koricanac G, Tepavcevic S, Stojiljkovic M, Milosavljevic T, Isenovic ER. Impairment of cardiac insulin signaling in fructose-fed ovariectomized female Wistar rats. Eur J Nutr 2011; 50: 543-551
    CrossrefPubMedGoogle Scholar
  • 6 Koricanac G, Tepavcevic S, Zakula Z, Milosavljevic T, Stojiljkovic M, Isenovic ER. Interference between insulin and estradiol signaling pathways in the regulation of cardiac eNOS and Na(+)/K(+)-ATPase. Eur J Pharmacol 2011; 655: 23-30
    CrossrefPubMedGoogle Scholar
  • 7 Tepavcevic S, Koricanac G, Zakula Z, Milosavljevic T, Stojiljkovic M, Isenovic ER. Interaction between insulin and estradiol in regulation of cardiac glucose and free fatty acid transporters. Horm Metab Res 2011; 43: 524-530
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Galipeau D, Verma S, McNeill JH. Female rats are protected against fructose-induced changes in metabolism and blood pressure. Am J Physiol Heart Circ Physiol 2002; 283: H2478-H2484
    CrossrefPubMedGoogle Scholar
  • 9 Galipeau DM, Yao L, McNeill JH. Relationship among hyperinsulinemia, insulin resistance, and hypertension is dependent on sex. Am J Physiol Heart Circ Physiol 2002; 283: H562-H567
    PubMedGoogle Scholar
  • 10 Vasudevan H, Xiang H, McNeill JH. Differential regulation of insulin resistance and hypertension by sex hormones in fructose-fed male rats. Am J Physiol Heart Circ Physiol 2005; 289: H1335-H1342
    CrossrefPubMedGoogle Scholar
  • 11 Busserolles J, Mazur A, Gueux E, Rock E, Rayssiguier Y. Metabolic syndrome in the rat: females are protected against the pro-oxidant effect of a high sucrose diet. Exp Biol Med (Maywood) 2002; 227: 837-842
    PubMedGoogle Scholar
  • 12 Sales S, Ureshino RP, Pereira RT, Luna MS, Pires de Oliveira M, Yamanouye N, Godinho RO, Smaili SS, Porto CS, Abdalla FM. Effects of 17beta-estradiol replacement on the apoptotic effects caused by ovariectomy in the rat hippocampus. Life Sci 2010; 86: 832-838
    CrossrefPubMedGoogle Scholar
  • 13 Carvalheira JB, Calegari VC, Zecchin HG, Nadruz Jr W, Guimaraes RB, Ribeiro EB, Franchini KG, Velloso LA, Saad MJ. The cross-talk between angiotensin and insulin differentially affects phosphatidylinositol 3-kinase- and mitogen-activated protein kinase mediated signaling in rat heart: implications for insulin resistance. Endocrinology 2003; 144: 5604-5614
    CrossrefPubMedGoogle Scholar
  • 14 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
    Google Scholar
  • 15 Dupont J, Derouet M, Simon J, Taouis M. Nutritional state regulates insulin receptor and IRS-1 phosphorylation and expression in chicken. Am J Physiol 1998; 274: E309-E316
    PubMedGoogle Scholar
  • 16 Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC. Measurement of protein using bicinchoninic acid. Anal Biochem 1985; 150: 76-85
    CrossrefPubMedGoogle Scholar
  • 17 Luiken JJ, Koonen DP, Willems J, Zorzano A, Becker C, Fischer Y, Tandon NN, Van Der Vusse GJ, Bonen A, Glatz JF. Insulin stimulates long-chain fatty acid utilization by rat cardiac myocytes through cellular redistribution of FAT/CD36. Diabetes 2002; 51: 3113-3119
    CrossrefPubMedGoogle Scholar
  • 18 Rosta K, Tulassay E, Enzsoly A, Ronai K, Szantho A, Pandics T, Fekete A, Mandl P, Ver A. Insulin induced translocation of Na+/K+ -ATPase is decreased in the heart of streptozotocin diabetic rats. Acta Pharmacol Sinica 2009; 30: 1616-1624
    CrossrefPubMedGoogle Scholar
  • 19 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-685
    CrossrefPubMedGoogle Scholar
  • 20 Koricanac G, Tepavcevic S, Romic S, Zivkovic M, Stojiljkovic M, Milosavljevic T, Stankovic A, Petkovic M, Kamceva T, Zakula Z. Estradiol enhances effects of fructose rich diet on cardiac fatty acid transporter CD36 and triglycerides accumulation. Eur J Pharmacol 2012; 694: 127-134
    CrossrefPubMedGoogle Scholar
  • 21 Iannello S, Milazzo P, Belfiore F. Animal and human tissue Na,K-ATPase in normal and insulin-resistant states: regulation, behaviour and interpretative hypothesis on NEFA effects. Obes Rev 2007; 8: 231-251
    CrossrefPubMedGoogle Scholar
  • 22 Rosic NK, Standaert ML, Pollet RJ. The mechanism of insulin stimulation of (Na+,K+) ATPase transport activity in muscle. J Biol Chem 1985; 260: 6206-6212
    PubMedGoogle Scholar
  • 23 Kelly RA, O’Hara DS, Mitch WE, Smith TW. Identification of NaK-ATPase inhibitors in human plasma as nonesterified fatty acids and lysophospholipids. J Biol Chem 1986; 261: 11704-11711
    PubMedGoogle Scholar
  • 24 Berger ME, Ormsby BL, Bunnag P, Hori MT, Tuck ML, Golub MS. Increased functional Na(+)-K+ pump activity in the vasculature of fructose-fed hyperinsulinemic and hypertensive rats. Hypertens Res 1998; 21: 73-80
    CrossrefPubMedGoogle Scholar
  • 25 Luiken JJ, Coort SL, Koonen DP, van der Horst DJ, Bonen A, Zorzano A, Glatz JF. Regulation of cardiac long-chain fatty acid and glucose uptake by translocation of substrate transporters. Pflugers Arch 2004; 448: 1-15
    CrossrefPubMedGoogle Scholar
  • 26 Qin B, Polansky MM, Harry D, Anderson RA. Green tea polyphenols improve cardiac muscle mRNA and protein levels of signal pathways related to insulin and lipid metabolism and inflammation in insulin-resistant rats. Mol Nutr Food Res 2010; 54 (Suppl. 01) S14-S23
    CrossrefPubMedGoogle Scholar
  • 27 Arias-Loza PA, Kreissl MC, Kneitz S, Kaiser FR, Israel I, Hu K, Frantz S, Bayer B, Fritzemeier KH, Korach KS, Pelzer T. The estrogen receptor-alpha is required and sufficient to maintain physiological glucose uptake in the mouse heart. Hypertension 2012; 60: 1070-1077
    CrossrefPubMedGoogle Scholar
  • 28 Dzurba A, Ziegelhoffer A, Vrbjar N, Styk J, Slezak J. Estradiol modulates the sodium pump in the heart sarcolemma. Mol Cell Biochem 1997; 176: 113-118
    CrossrefPubMedGoogle Scholar
  • 29 Liu CG, Xu KQ, Xu X, Huang JJ, Xiao JC, Zhang JP, Song HP. 17Beta-oestradiol regulates the expression of Na+/K+-ATPase beta1-subunit, sarcoplasmic reticulum Ca2+ ATPase and carbonic anhydrase iv in H9C2 cells. Clin Exp Pharmacol Physiol 2007; 34: 998-1004
    CrossrefPubMedGoogle Scholar