{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T12:06:20Z","timestamp":1774526780149,"version":"3.50.1"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,4,24]],"date-time":"2018-04-24T00:00:00Z","timestamp":1524528000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,4,24]],"date-time":"2018-04-24T00:00:00Z","timestamp":1524528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>GLUT transgenic and knockout mice have provided valuable insight into the role of facilitative glucose transporters (GLUTs) in cardiovascular and metabolic disease, but compensatory physiological changes can hinder interpretation of these models. To determine whether adaptations occur in response to GLUT inhibition in the failing adult heart, we chronically treated TG9 mice, a transgenic model of dilated cardiomyopathy and heart failure, with the GLUT inhibitor ritonavir. Glucose tolerance was significantly improved with chronic treatment and correlated with decreased adipose tissue retinol binding protein 4 (RBP4) and resistin. A modest improvement in lifespan was associated with decreased cardiomyocyte brain natriuretic peptide <jats:bold>(<\/jats:bold>BNP) expression, a marker of heart failure severity. GLUT1 and \u221212 protein expression was significantly increased in left ventricular (LV) myocardium in ritonavir-treated animals. Supporting a switch from fatty acid to glucose utilization in these tissues, fatty acid transporter CD36 and fatty acid transcriptional regulator peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1) mRNA were also decreased in LV and soleus muscle. Chronic ritonavir also increased cardiac output and dV\/dt-d in C57Bl\/6 mice following ischemia-reperfusion injury. Taken together, these data demonstrate compensatory metabolic adaptation in response to chronic GLUT blockade as a means to evade deleterious changes in the failing heart.<\/jats:p>","DOI":"10.1038\/s41598-018-24867-1","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T13:56:14Z","timestamp":1524059774000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Metabolic and Cardiac Adaptation to Chronic Pharmacologic Blockade of Facilitative Glucose Transport in Murine Dilated Cardiomyopathy and Myocardial Ischemia"],"prefix":"10.1038","volume":"8","author":[{"given":"Monique R.","family":"Heitmeier","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria A.","family":"Payne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Weinheimer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Attila","family":"Kovacs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard C.","family":"Hresko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick Y.","family":"Jay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul W.","family":"Hruz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,4,24]]},"reference":[{"key":"24867_CR1","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1161\/CIRCRESAHA.113.300376","volume":"113","author":"T Doenst","year":"2013","unstructured":"Doenst, T., Nguyen, T. D. & Abel, E. D. Cardiac metabolism in heart failure: implications beyond ATP production. Circ Res 113, 709\u2013724 (2013).","journal-title":"Circ Res"},{"key":"24867_CR2","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1161\/CIRCRESAHA.116.306206","volume":"118","author":"C Riehle","year":"2016","unstructured":"Riehle, C. & Abel, E. D. Insulin Signaling and Heart Failure. Circulation Research 118, 1151\u20131169 (2016).","journal-title":"Circulation Research"},{"key":"24867_CR3","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1161\/CIRCULATIONAHA.107.702795","volume":"116","author":"H Ashrafian","year":"2007","unstructured":"Ashrafian, H., Frenneaux, M. P. & Opie, L. H. Metabolic Mechanisms in Heart Failure. Circulation 116, 434\u2013448 (2007).","journal-title":"Circulation"},{"key":"24867_CR4","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/nrendo.2015.216","volume":"12","author":"G Jia","year":"2016","unstructured":"Jia, G., DeMarco, V. G. & Sowers, J. R. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy. Nature reviews. Endocrinology 12, 144\u2013153 (2016).","journal-title":"Nature reviews. Endocrinology"},{"key":"24867_CR5","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.mam.2012.07.001","volume":"34","author":"M Mueckler","year":"2013","unstructured":"Mueckler, M. & Thorens, B. The SLC2 (GLUT) family of membrane transporters. Mol Aspects Med 34, 121\u2013138 (2013).","journal-title":"Mol Aspects Med"},{"key":"24867_CR6","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.1161\/01.CIR.0000034049.61181.F3","volume":"106","author":"R Liao","year":"2002","unstructured":"Liao, R. et al. Cardiac-specific overexpression of GLUT1 prevents the development of heart failure attributable to pressure overload in mice. Circulation 106, 2125\u20132131 (2002).","journal-title":"Circulation"},{"key":"24867_CR7","doi-asserted-by":"publisher","first-page":"2818","DOI":"10.1161\/CIRCULATIONAHA.108.832915","volume":"119","author":"J Yan","year":"2009","unstructured":"Yan, J. et al. Increased glucose uptake and oxidation in mouse hearts prevent high fatty acid oxidation but cause cardiac dysfunction in diet-induced obesity. Circulation 119, 2818\u20132828 (2009).","journal-title":"Circulation"},{"key":"24867_CR8","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/377151a0","volume":"377","author":"EB Katz","year":"1995","unstructured":"Katz, E. B., Stenbit, A. E., Hatton, K., DePinho, R. & Charron, M. J. Cardiac and adipose tissue abnormalities but not diabetes in mice deficient in GLUT4. Nature 377, 151\u2013155 (1995).","journal-title":"Nature"},{"key":"24867_CR9","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1172\/JCI7605","volume":"104","author":"ED Abel","year":"1999","unstructured":"Abel, E. D. et al. Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart. J Clin Invest 104, 1703\u20131714 (1999).","journal-title":"J Clin Invest"},{"key":"24867_CR10","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/1475-2840-11-63","volume":"11","author":"L Aerni-Flessner","year":"2012","unstructured":"Aerni-Flessner, L., Abi-Jaoude, M., Koenig, A., Payne, M. & Hruz, P. W. GLUT4, GLUT1, and GLUT8 are the dominant GLUT transcripts expressed in the murine left ventricle. Cardiovasc Diabetol 11, 63 (2012).","journal-title":"Cardiovasc Diabetol"},{"key":"24867_CR11","doi-asserted-by":"publisher","first-page":"R1300","DOI":"10.1152\/ajpregu.00822.2010","volume":"301","author":"B Ware","year":"2011","unstructured":"Ware, B. et al. Chronic heart failure selectively induces regional heterogeneity of insulin-responsive glucose transporters. Am J Physiol Regul Integr Comp Physiol 301, R1300\u20131306 (2011).","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"24867_CR12","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.2337\/db11-0033","volume":"60","author":"SH Purcell","year":"2011","unstructured":"Purcell, S. H. et al. Improved insulin sensitivity by GLUT12 overexpression in mice. Diabetes 60, 1478\u20131482 (2011).","journal-title":"Diabetes"},{"key":"24867_CR13","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1097\/01.qai.0000176654.97392.c7","volume":"40","author":"Q Yan","year":"2005","unstructured":"Yan, Q. & Hruz, P. W. Direct comparison of the acute in vivo effects of HIV protease inhibitors on peripheral glucose disposal. J Acquir Immune Defic Syndr 40, 398\u2013403 (2005).","journal-title":"J Acquir Immune Defic Syndr"},{"key":"24867_CR14","doi-asserted-by":"publisher","first-page":"20251","DOI":"10.1074\/jbc.C000228200","volume":"275","author":"H Murata","year":"2000","unstructured":"Murata, H., Hruz, P. W. & Mueckler, M. The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem 275, 20251\u201320254 (2000).","journal-title":"J Biol Chem"},{"key":"24867_CR15","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1097\/00002030-200204120-00005","volume":"16","author":"H Murata","year":"2002","unstructured":"Murata, H., Hruz, P. W. & Mueckler, M. Indinavir inhibits the glucose transporter isoform Glut4 at physiologic concentrations. AIDS 16, 859\u2013863 (2002).","journal-title":"AIDS"},{"key":"24867_CR16","doi-asserted-by":"publisher","first-page":"e25237","DOI":"10.1371\/journal.pone.0025237","volume":"6","author":"RC Hresko","year":"2011","unstructured":"Hresko, R. C. & Hruz, P. W. HIV protease inhibitors act as competitive inhibitors of the cytoplasmic glucose binding site of GLUTs with differing affinities for GLUT1 and GLUT4. PLoS One 6, e25237 (2011).","journal-title":"PLoS One"},{"key":"24867_CR17","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1001\/jama.2010.1004","volume":"304","author":"MA Thompson","year":"2010","unstructured":"Thompson, M. A. et al. Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel. JAMA 304, 321\u2013333 (2010).","journal-title":"JAMA"},{"key":"24867_CR18","doi-asserted-by":"publisher","first-page":"937","DOI":"10.2337\/diabetes.51.4.937","volume":"51","author":"PW Hruz","year":"2002","unstructured":"Hruz, P. W., Murata, H., Qiu, H. & Mueckler, M. Indinavir induces acute and reversible peripheral insulin resistance in rats. Diabetes 51, 937\u2013942 (2002).","journal-title":"Diabetes"},{"key":"24867_CR19","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.beem.2010.10.017","volume":"25","author":"PW Hruz","year":"2011","unstructured":"Hruz, P. W. Molecular mechanisms for insulin resistance in treated HIV-infection. Best Pract Res Clin Endocrinol Metab 25, 459\u2013468 (2011).","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"24867_CR20","doi-asserted-by":"publisher","first-page":"e20","DOI":"10.1161\/CIRCULATIONAHA.107.189623","volume":"118","author":"C Grunfeld","year":"2008","unstructured":"Grunfeld, C. et al. Contribution of Metabolic and Anthropometric Abnormalities to Cardiovascular Disease Risk Factors. Circulation 118, e20\u201328 (2008).","journal-title":"Circulation"},{"key":"24867_CR21","doi-asserted-by":"publisher","first-page":"F1","DOI":"10.1097\/00002030-200203290-00002","volume":"16","author":"MA Noor","year":"2002","unstructured":"Noor, M. A. et al. Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: a randomized, placebo-controlled study. AIDS 16, F1\u2013F8 (2002).","journal-title":"AIDS"},{"key":"24867_CR22","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.2337\/diabetes.52.7.1695","volume":"52","author":"JC Koster","year":"2003","unstructured":"Koster, J. C., Remedi, M. S., Qiu, H., Nichols, C. G. & Hruz, P. W. HIV protease inhibitors acutely impair glucose-stimulated insulin release. Diabetes 52, 1695\u20131700 (2003).","journal-title":"Diabetes"},{"key":"24867_CR23","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1097\/QAD.0b013e32826fbc54","volume":"21","author":"GA Lee","year":"2007","unstructured":"Lee, G. A. et al. Effects of ritonavir and amprenavir on insulin sensitivity in healthy volunteers. AIDS 21, 2183\u20132190 (2007).","journal-title":"AIDS"},{"key":"24867_CR24","doi-asserted-by":"publisher","first-page":"2161","DOI":"10.1096\/fj.07-102269","volume":"22","author":"PW Hruz","year":"2008","unstructured":"Hruz, P. W., Yan, Q., Struthers, H. & Jay, P. Y. HIV protease inhibitors that block GLUT4 precipitate acute, decompensated heart failure in a mouse model of dilated cardiomyopathy. FASEB J 22, 2161\u20132167 (2008).","journal-title":"FASEB J"},{"key":"24867_CR25","doi-asserted-by":"publisher","first-page":"e17178","DOI":"10.1371\/journal.pone.0017178","volume":"6","author":"AK Vyas","year":"2011","unstructured":"Vyas, A. K. et al. Exenatide improves glucose homeostasis and prolongs survival in a murine model of dilated cardiomyopathy. PLoS One 6, e17178 (2011).","journal-title":"PLoS One"},{"key":"24867_CR26","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.cardfail.2006.03.002","volume":"12","author":"A Buerger","year":"2006","unstructured":"Buerger, A. et al. Dilated cardiomyopathy resulting from high-level myocardial expression of Cre-recombinase. J Card Fail 12, 392\u2013398 (2006).","journal-title":"J Card Fail"},{"key":"24867_CR27","doi-asserted-by":"crossref","first-page":"7407","DOI":"10.1128\/AAC.00218-16","volume":"60","author":"TE Kraft","year":"2016","unstructured":"Kraft, T. E. et al. A Novel Fluorescence Resonance Energy Transfer-Based Screen in High-Throughput Format To Identify Inhibitors of Malarial and Human Glucose Transporters. Antimicrob Agents Chemother 60, 7407\u20137414 (2016).","journal-title":"Antimicrob Agents Chemother"},{"key":"24867_CR28","doi-asserted-by":"crossref","unstructured":"House, S. L. et al. Fibroblast growth factor 2 is an essential cardioprotective factor in a closed\u2010chest model of cardiac ischemia\u2010reperfusion injury. Physiological Reports 3 (2015).","DOI":"10.14814\/phy2.12278"},{"key":"24867_CR29","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-11-80","volume":"11","author":"P Gupta","year":"2013","unstructured":"Gupta, P. et al. Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced myocardial necrosis: a new therapeutic implication. Journal of translational medicine 11, 80 (2013).","journal-title":"Journal of translational medicine"},{"key":"24867_CR30","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1073\/pnas.0336724100","volume":"100","author":"BN Finck","year":"2003","unstructured":"Finck, B. N. et al. A critical role for PPARalpha-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: modulation by dietary fat content. Proc Natl Acad Sci USA 100, 1226\u20131231 (2003).","journal-title":"Proc Natl Acad Sci USA"},{"key":"24867_CR31","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1172\/JCI0214080","volume":"109","author":"BN Finck","year":"2002","unstructured":"Finck, B. N. et al. The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest 109, 121\u2013130 (2002).","journal-title":"J Clin Invest"},{"key":"24867_CR32","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1161\/01.RES.0000264104.25265.b6","volume":"100","author":"J Yang","year":"2007","unstructured":"Yang, J. et al. CD36 deficiency rescues lipotoxic cardiomyopathy. Circ Res 100, 1208\u20131217 (2007).","journal-title":"Circ Res"},{"key":"24867_CR33","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.cmet.2005.01.006","volume":"1","author":"BN Finck","year":"2005","unstructured":"Finck, B. N. et al. A potential link between muscle peroxisome proliferator- activated receptor-alpha signaling and obesity-related diabetes. Cell Metab 1, 133\u2013144 (2005).","journal-title":"Cell Metab"},{"key":"24867_CR34","doi-asserted-by":"publisher","first-page":"2548","DOI":"10.1210\/jc.2004-0395","volume":"89","author":"EE Kershaw","year":"2004","unstructured":"Kershaw, E. E. & Flier, J. S. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89, 2548\u20132556 (2004).","journal-title":"J Clin Endocrinol Metab"},{"key":"24867_CR35","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.bbadis.2012.09.013","volume":"1832","author":"AP Waller","year":"2013","unstructured":"Waller, A. P. et al. GLUT12 functions as a basal and insulin-independent glucose transporter in the heart. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1832, 121\u2013127 (2013).","journal-title":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease"},{"key":"24867_CR36","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1007\/s00125-014-3171-6","volume":"57","author":"H Bugger","year":"2014","unstructured":"Bugger, H. & Abel, E. D. Molecular mechanisms of diabetic cardiomyopathy. Diabetologia 57, 660\u2013671 (2014).","journal-title":"Diabetologia"},{"key":"24867_CR37","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1097\/00002030-200305230-00010","volume":"17","author":"N Friis-Moller","year":"2003","unstructured":"Friis-Moller, N. et al. Cardiovascular disease risk factors in HIV patients\u2013association with antiretroviral therapy. Results from the DAD study. AIDS 17, 1179\u20131193 (2003).","journal-title":"AIDS"},{"key":"24867_CR38","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1001\/archinternmed.2010.197","volume":"170","author":"S Lang","year":"2010","unstructured":"Lang, S. et al. Impact of individual antiretroviral drugs on the risk of myocardial infarction in human immunodeficiency virus-infected patients: a case-control study nested within the French Hospital Database on HIV ANRS cohort CO4. Arch Intern Med 170, 1228\u20131238 (2010).","journal-title":"Arch Intern Med"},{"key":"24867_CR39","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1111\/j.1559-4572.2008.07635.x","volume":"3","author":"TS Sharma","year":"2008","unstructured":"Sharma, T. S., Messiah, S., Fisher, S., Miller, T. L. & Lipshultz, S. E. Accelerated cardiovascular disease and myocardial infarction risk in patients with the human immunodeficiency virus. Journal of the cardiometabolic syndrome 3, 93\u201397 (2008).","journal-title":"Journal of the cardiometabolic syndrome"},{"key":"24867_CR40","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1160\/TH05-07-0514","volume":"96","author":"R Bhindi","year":"2006","unstructured":"Bhindi, R., Witting, P. K., McMahon, A. C., Khachigian, L. M. & Lowe, H. C. Rat models of myocardial infarction - Pathogenetic insights and clinical relevance. Thrombosis and haemostasis 96, 602\u2013610 (2006).","journal-title":"Thrombosis and haemostasis"},{"key":"24867_CR41","first-page":"489","volume":"25","author":"JF Denissen","year":"1997","unstructured":"Denissen, J. F. et al. Metabolism And Disposition of the HIV-1 Protease Inhibitor Ritonavir (ABT-538) in Rats, Dogs, and Humans. Drug Metab Dispos 25, 489\u2013489 (1997).","journal-title":"Drug Metab Dispos"},{"key":"24867_CR42","first-page":"8","volume":"5","author":"M Noor","year":"2000","unstructured":"Noor, M. et al. Metabolic effects of indinavir in healthy HIV-seronegative subjects. Antivir Ther 5, 8 (2000).","journal-title":"Antivir Ther"},{"key":"24867_CR43","doi-asserted-by":"publisher","first-page":"E558","DOI":"10.1152\/ajpendo.00167.2007","volume":"294","author":"MJ Carper","year":"2008","unstructured":"Carper, M. J. et al. HIV-protease inhibitors induce expression of suppressor of cytokine signaling-1 in insulin-sensitive tissues and promote insulin resistance and type 2 diabetes mellitus. Am J Physiol Endocrinol Metab 294, E558\u2013567 (2008).","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"24867_CR44","doi-asserted-by":"publisher","first-page":"3474","DOI":"10.2337\/diabetes.54.12.3474","volume":"54","author":"SB Haugaard","year":"2005","unstructured":"Haugaard, S. B. et al. Skeletal muscle insulin signaling defects downstream of phosphatidylinositol 3-kinase at the level of Akt are associated with impaired nonoxidative glucose disposal in HIV lipodystrophy. Diabetes 54, 3474\u20133483 (2005).","journal-title":"Diabetes"},{"key":"24867_CR45","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1086\/505974","volume":"43","author":"GA Lee","year":"2006","unstructured":"Lee, G. A. et al. Single-dose lopinavir-ritonavir acutely inhibits insulin-mediated glucose disposal in healthy volunteers. Clin Infect Dis 43, 658\u2013660 (2006).","journal-title":"Clin Infect Dis"},{"key":"24867_CR46","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1177\/135965350801300215","volume":"13","author":"AN Phillips","year":"2008","unstructured":"Phillips, A. N. et al. Interruption of antiretroviral therapy and risk of cardiovascular disease in persons with HIV-1 infection: exploratory analyses from the SMART trial. Antivir Ther 13, 177\u2013187 (2008).","journal-title":"Antivir Ther"},{"key":"24867_CR47","doi-asserted-by":"publisher","first-page":"e000343","DOI":"10.1161\/JAHA.113.000343","volume":"2","author":"KJ Lavine","year":"2013","unstructured":"Lavine, K. J., Kovacs, A., Weinheimer, C. & Mann, D. L. Repetitive myocardial ischemia promotes coronary growth in the adult mammalian heart. Journal of the American Heart Association 2, e000343 (2013).","journal-title":"Journal of the American Heart Association"},{"key":"24867_CR48","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1097\/XCE.0b013e32835bfb24","volume":"1","author":"A Kalla Vyas","year":"2012","unstructured":"Kalla Vyas, A. et al. Saxagliptin improves glucose tolerance but not survival in a murine model of dilated cardiomyopathy. Cardiovascular Endocrinology 1, 74\u201382, https:\/\/doi.org\/10.1097\/XCE.1090b1013e32835bfb32824 (2012).","journal-title":"Cardiovascular Endocrinology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-24867-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-24867-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-24867-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T04:33:49Z","timestamp":1671597229000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-24867-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,24]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["24867"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-24867-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,24]]},"assertion":[{"value":"7 September 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 April 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"6475"}}