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DOI: 10.1055/s-0031-1280784
Interaction Between Insulin and Estradiol in Regulation of Cardiac Glucose and Free Fatty Acid Transporters
Publikationsverlauf
received 20. Dezember 2010
accepted 25. Mai 2011
Publikationsdatum:
19. Juli 2011 (online)
![](https://www.thieme-connect.de/media/hmr/201108/lookinside/thumbnails/10.1055-s-0031-1280784-1.jpg)
Abstract
The estrogen binding to specific extranuclear receptors (ER) activates several intracellular pathways that are activated by insulin as well. Moreover, insulin and estradiol (E2) influence cardiac energy substrates, blood glucose and free fatty acids (FFAs), and both hormones exert cardio-beneficial effects. In view of these facts, we suggest that cross-talk between their signaling pathways might have an important role in regulation of cardiac energy substrate transport. Ovariectomized rats were treated with insulin, estradiol (E2), or their combination 20, 30, or 40 min before analysis of blood glucose and FFA level, as well as cardiac plasma membranes (PM) and low density microsomes (LDM) content of glucose (GLUT4 and GLUT1) and FFA (CD36) transporters. Insulin, given alone, or in combination with E2, decreased plasma glucose level at all time points, but did not influence FFA level, while E2 treatment itself did not change glucose and FFA concentration. Insulin increased PM GLUT4 and GLUT1 content 30 and 40 min after treatment and the increases were partially accompanied by decrease in transporter LDM content. E2 increased PM content and decreased LDM content only of GLUT4 at 30 min. Insulin generally, and E2 at 20 min increased CD36 content in PM fraction. Both hormones decreased CD36 LDM content 20 min after administration. Effect of combined treatment mostly did not differ from single hormone treatment, but occasionally, particularly in distribution of GLUT4, combined treatment emphasized single hormone effect, suggesting that insulin and E2 act synergistically in regulation of energy substrate transporters in cardiac tissue.
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References
- 1 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
- 2 Zorzano A, Sevilla L, Camps M, Becker C, Meyer J, Kammermeier H, Munoz P, Guma A, Testar X, Palacin M, Blasi J, Fischer Y. Regulation of glucose transport, and glucose transporters expression and trafficking in the heart: studies in cardiac myocytes. Am J Cardiol 1997; 80: 65A-76A
- 3 Chabowski A, Coort SL, Calles-Escandon J, Tandon NN, Glatz JF, Luiken JJ, Bonen A. Insulin stimulates fatty acid transport by regulating expression of FAT/CD36 but not FABPpm. Am J Physiol Endocrinol Metab 2004; 287: E781-E789
- 4 Bertrand L, Horman S, Beauloye C, Vanoverschelde JL. Insulin signalling in the heart. Cardiovasc Res 2008; 79: 238-248
- 5 Brown L, Hoong I, Doggrell SA. The heart as a target for oestrogens. Heart Lung Circ 2000; 9: 113-125
- 6 Patten RD, Pourati I, Aronovitz MJ, Baur J, Celestin F, Chen X, Michael A, Haq S, Nuedling S, Grohe C, Force T, Mendelsohn ME, Karas RH. 17beta-estradiol reduces cardiomyocyte apoptosis in vivo and in vitro via activation of phospho-inositide-3 kinase/Akt signaling. Circ Res 2004; 95: 692-699
- 7 Kim JK, Levin ER. Estrogen signaling in the cardiovascular system. Nucl Recept Signal 2006; 4: e013
- 8 Patten RD, Karas RH. Estrogen replacement and cardiomyocyte protection. Trends Cardiovasc Med 2006; 16: 69-75
- 9 Jensen MD, Martin ML, Cryer PE, Roust LR. Effects of estrogen on free fatty acid metabolism in humans. Am J Physiol 1994; 266: E914-E920
- 10 Sugaya A, Sugiyama T, Yanase S, Terada Y, Toyoda N. Glucose transporter 4 (GLUT4) mRNA abundance in the adipose tissue and skeletal-muscle tissue of ovariectomized rats treated with 17 beta-estradiol or progesterone. J Obstet Gynaecol Res 1999; 25: 9-14
- 11 Cheng CM, Cohen M, Wang J, Bondy CA. Estrogen augments glucose transporter and IGF1 expression in primate cerebral cortex. FASEB J 2001; 15: 907-915
- 12 Welch RD, Gorski J. Regulation of glucose transporters by estradiol in the immature rat uterus. Endocrinology 1999; 140: 3602-3608
- 13 Hsieh YC, Choudhry MA, Yu HP, Shimizu T, Yang S, Suzuki T, Chen J, Bland KI, Chaudry IH. Inhibition of cardiac PGC-1alpha expression abolishes ERbeta agonist-mediated cardioprotection following trauma-hemorrhage. FASEB J 2006; 20: 1109-1117
- 14 Novotny JL, Simpson AM, Tomicek NJ, Lancaster TS, Korzick DH. Rapid estrogen receptor-alpha activation improves ischemic tolerance in aged female rats through a novel protein kinase C epsilon-dependent mechanism. Endocrinology 2009; 150: 889-896
- 15 Levin ER. Plasma membrane estrogen receptors. Trends Endocrinol Metab 2009; 20: 477-482
- 16 Pedram A, Razandi M, Aitkenhead M, Levin ER. Estrogen inhibits cardiomyocyte hypertrophy in vitro. Antagonism of calcineurin-related hypertrophy through induction of MCIP1. J Biol Chem 2005; 280: 26339-26348
- 17 Abel ED. Insulin signaling in heart muscle: lessons from genetically engineered mouse models. Curr Hypertens Rep 2004; 6: 416-423
- 18 Alonso A, Gonzalez C. Relationship between non-genomic actions of estrogens and insulin resistace. Infect Disord Drug Targets 2008; 8: 48-51
- 19 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
- 20 Nuedling S, Kahlert S, Loebbert K, Doevendans PA, Meyer R, Vetter H, Grohe C. 17 Beta-estradiol stimulates expression of endothelial and inducible NO synthase in rat myocardium in-vitro and in-vivo. Cardiovasc Res 1999; 43: 666-674
- 21 Wang L, Gout I, Proud CG. Cross-talk between the ERK and p70 S6 kinase (S6K) signaling pathways. MEK-dependent activation of S6K2 in cardiomyocytes. J Biol Chem 2001; 276: 32670-32677
- 22 Duncombe WG. The colorimetric micro-determination of non-esterified fatty acids in plasma. Clin Chim Acta 1964; 9: 122-125
- 23 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
- 24 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
- 25 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
- 26 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-685
- 27 Kodde IF, van der Stok J, Smolenski RT, de Jong JW. Metabolic and genetic regulation of cardiac energy substrate preference. Comp Biochem Physiol A Mol Integr Physiol 2007; 146: 26-39
- 28 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
- 29 Mannella P, Brinton RD. Estrogen receptor protein interaction with phosphatidylinositol 3-kinase leads to activation of phosphorylated Akt and extracellular signal-regulated kinase 1/2 in the same population of cortical neurons: a unified mechanism of estrogen action. J Neurosci 2006; 26: 9439-9447
- 30 Zierath JR, Wallberg-Henriksson H. From receptor to effector: insulin signal transduction in skeletal muscle from type II diabetic patients. Ann NY Acad Sci 2002; 967: 120-134
- 31 Koricanac G, Milosavljevic T, Stojiljkovic M, Zakula Z, Tepavcevic S, Ribarac-Stepic N, Isenovic ER. Impact of estradiol on insulin signaling in the rat heart. Cell Biochem Funct 2009; 27: 102-110
- 32 Fischer Y, Thomas J, Sevilla L, Munoz P, Becker C, Holman G, Kozka IJ, Palacin M, Testar X, Kammermeier H, Zorzano A. Insulin-induced recruitment of glucose transporter 4 (GLUT4) and GLUT1 in isolated rat cardiac myocytes. Evidence of the existence of different intracellular GLUT4 vesicle populations. J Biol Chem 1997; 272: 7085-7092
- 33 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
- 34 Egert S, Nguyen N, Schwaiger M. Myocardial glucose transporter GLUT1: translocation induced by insulin and ischemia. J Mol Cell Cardiol 1999; 31: 1337-1344
- 35 Laybutt DR, Thompson AL, Cooney GJ, Kraegen EW. Selective chronic regulation of GLUT1 and GLUT4 content by insulin, glucose, and lipid in rat cardiac muscle in vivo. Am J Physiol 1997; 273: H1309-H1316
- 36 Becker C, Sevilla L, Tomas E, Palacin M, Zorzano A, Fischer Y. The endosomal compartment is an insulin-sensitive recruitment site for GLUT4 and GLUT1 glucose transporters in cardiac myocytes. Endocrinology 2001; 142: 5267-5276
- 37 Kessler A, Uphues I, Ouwens DM, Till M, Eckel J. Diversification of cardiac insulin signaling involves the p85 alpha/beta subunits of phosphatidylinositol 3-kinase. Am J Physiol Endocrinol Metab 2001; 280: E65-E74
- 38 Barros RP, Machado UF, Warner M, Gustafsson JA. Muscle GLUT4 regulation by estrogen receptors ERbeta and ERalpha. Proc Natl Acad Sci USA 2006; 103: 1605-1608