{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:48:02Z","timestamp":1783698482902,"version":"3.55.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["Agreement No. 075-15-2020-901"],"award-info":[{"award-number":["Agreement No. 075-15-2020-901"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["Agreement No. 075-15-2020-901"],"award-info":[{"award-number":["Agreement No. 075-15-2020-901"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["Agreement No. 075-15-2020-901"],"award-info":[{"award-number":["Agreement No. 075-15-2020-901"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["Agreement No. 075-15-2020-901"],"award-info":[{"award-number":["Agreement No. 075-15-2020-901"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["Agreement No. 075-15-2020-901"],"award-info":[{"award-number":["Agreement No. 075-15-2020-901"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Impaired glucose tolerance (IGT) increases cardiovascular risk and can enlarge myocardial infarction (MI) incidence and severity. There is lack of information about cardioprotective potential of glucose-lowering drugs in IGT. We aimed to evaluate the sustainability of myocardium to ischemia\u2013reperfusion injury in diabetic and IGT rats and to study cardioprotective action of metformin and liraglutide. Type 2 diabetes mellitus (DM) and IGT were modelled in Wistar rats by high-fat diet and streptozotocin\u2009+\u2009nicotinamide. 4\u00a0weeks after rats were divided into 4 groups: DM (without treatment) (n\u2009=\u20094), IGT (without treatment) (n\u2009=\u20094), IGT\u2009+\u2009MET (metformin 200\u00a0mg\/kg per os once daily 8\u00a0weeks) (n\u2009=\u20094), IGT\u2009+\u2009LIRA (liraglutide 0.06\u00a0mg\/kg s.c. once daily for 8\u00a0weeks) (n\u2009=\u20094). Control (n\u2009=\u20096) and high-fat diet (n\u2009=\u20098) groups were made for comparison. After 8\u00a0weeks ischemia\u2013reperfusion injury in isolated hearts was performed. Hemodynamic parameters were evaluated and MI size was measured by staining of myocardium slices in triphenyltetrazolium chloride solution. Blood glucose level was measured during the study. Both IGT and DM led to similar worsening of hemodynamic parameters during ischemia\u2013reperfusion period, in comparison with control group. MI size in IGT (56.76 (51.58; 69.07) %) and DM (57.26 (45.51; 70.08) %) groups was significantly larger than that in control group (42.98 (33.26; 61.84) %) and did not differ between each other. MI size in high-fat\u00a0diet group (56.98 (47.11; 62.83) %) was as large as in IGT and DM groups (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05). MI size in IGT\u2009+\u2009MET (42.11 (38.08; 71.96) %) and IGT\u2009+\u2009LIRA (42.50 (31.37; 60.40) %) was smaller than in both DM and IGT groups (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 for multiple comparison). Myocardium damage size did not differ in IGT\u2009+\u2009MET and IGT\u2009+\u2009LIRA groups (<jats:italic>p<\/jats:italic>\u2009&gt;\u2009\u00a00.05). Only LIRA, but not MET administration to IGT rats led to ischemic contracture reduction. Glycemic control was similarly satisfactory in IGT, IGT\u2009+\u2009MET, IGT\u2009+\u2009LIRA groups. Thus,\u00a0IGT and DM have similarly pronounced negative influence on hemodynamics and MI size in rat transient global ischemia ex vivo. Obesity development also has negative impact on the MI size. Both MET and LIRA have infarct-limiting effect independent on their influence on glucose level. LIRA, but not MET, diminishes ischemic contracture in IGT rats.<\/jats:p>","DOI":"10.1038\/s41598-021-86132-2","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T11:04:44Z","timestamp":1616497484000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Comparative evaluation of metformin and liraglutide cardioprotective effect in rats with impaired glucose tolerance"],"prefix":"10.1038","volume":"11","author":[{"given":"Anna","family":"Simanenkova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarkis","family":"Minasian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Karonova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timur","family":"Vlasov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya","family":"Timkina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oksana","family":"Shpilevaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Khalzova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anzhelika","family":"Shimshilashvili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Timofeeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniil","family":"Samsonov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yury","family":"Borshchev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Galagudza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,23]]},"reference":[{"key":"86132_CR1","unstructured":"IDF Diabetes Atlas. https:\/\/diabetesatlas.org\/data\/en\/world\/. Accessed 19 November 2020."},{"key":"86132_CR2","doi-asserted-by":"publisher","first-page":"4301461","DOI":"10.1155\/2017\/4301461","volume":"2017","author":"PF Shan","year":"2017","unstructured":"Shan, P. F., Li, Q., Khamaisi, M. & Qiang, G. F. Type 2 diabetes mellitus and macrovascular complications. Int. J. Endocrinol. 2017, 4301461. https:\/\/doi.org\/10.1155\/2017\/4301461 (2017).","journal-title":"Int. J. Endocrinol."},{"issue":"5","key":"86132_CR3","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/j.lpm.2013.02.313","volume":"42","author":"JL Schlienger","year":"2013","unstructured":"Schlienger, J. L. Complications du diab\u00e8te de type 2 [Type 2 diabetes complications]. Presse Med. 42(5), 839\u2013848 (2013).","journal-title":"Presse Med."},{"issue":"2","key":"86132_CR4","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/nrendo.2017.151","volume":"14","author":"Y Zheng","year":"2018","unstructured":"Zheng, Y., Ley, S. H. & Hu, F. B. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat. Rev. Endocrinol. 14(2), 88\u201398 (2018).","journal-title":"Nat. Rev. Endocrinol."},{"issue":"10085","key":"86132_CR5","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1016\/S0140-6736(17)30058-2","volume":"389","author":"S Chatterjee","year":"2017","unstructured":"Chatterjee, S., Khunti, K. & Davies, M. J. Type 2 diabetes. Lancet 389(10085), 2239\u20132251 (2017).","journal-title":"Lancet"},{"key":"86132_CR6","doi-asserted-by":"publisher","first-page":"i5953","DOI":"10.1136\/bmj.i5953","volume":"355","author":"Y Huang","year":"2016","unstructured":"Huang, Y., Cai, X., Mai, W., Li, M. & Hu, Y. Association between prediabetes and risk of cardiovascular disease and all cause mortality: systematic review and meta-analysis. BMJ 355, i5953. https:\/\/doi.org\/10.1136\/bmj.i5953 (2016).","journal-title":"BMJ"},{"issue":"13","key":"86132_CR7","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1016\/j.jacc.2009.10.060","volume":"55","author":"ES Ford","year":"2010","unstructured":"Ford, E. S., Zhao, G. & Li, C. Pre-diabetes and the risk for cardiovascular disease: a systematic review of the evidence. J. Am. Coll. Cardiol. 55(13), 1310\u20131317 (2010).","journal-title":"J. Am. Coll. Cardiol."},{"issue":"2","key":"86132_CR8","doi-asserted-by":"publisher","first-page":"233","DOI":"10.2337\/diacare.22.2.233","volume":"22","author":"M Coutinho","year":"1999","unstructured":"Coutinho, M., Gerstein, H. C., Wang, Y. & Yusuf, S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care 22(2), 233\u2013240 (1999).","journal-title":"Diabetes Care"},{"issue":"6","key":"86132_CR9","doi-asserted-by":"publisher","first-page":"920","DOI":"10.2337\/diacare.22.6.920","volume":"22","author":"M Tominaga","year":"1999","unstructured":"Tominaga, M. et al. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study. Diabetes Care 22(6), 920\u2013924 (1999).","journal-title":"Diabetes Care"},{"issue":"9324","key":"86132_CR10","doi-asserted-by":"publisher","first-page":"2140","DOI":"10.1016\/S0140-6736(02)09089-X","volume":"359","author":"A Norhammar","year":"2002","unstructured":"Norhammar, A. et al. Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study. Lancet 359(9324), 2140\u20132144 (2002).","journal-title":"Lancet"},{"issue":"22","key":"86132_CR11","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1016\/j.ehj.2004.09.021","volume":"25","author":"M Bartnik","year":"2004","unstructured":"Bartnik, M. et al. Newly detected abnormal glucose tolerance: an important predictor of long-term outcome after myocardial infarction. Eur. Heart J. 25(22), 1990\u20131997 (2004).","journal-title":"Eur. Heart J."},{"key":"86132_CR12","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/1475-2840-2-9","volume":"2","author":"D Lundblad","year":"2003","unstructured":"Lundblad, D. & Eliasson, M. Silent myocardial infarction in women with impaired glucose tolerance: the Northern Sweden MONICA study. Cardiovasc. Diabetol. 2, 9 (2003).","journal-title":"Cardiovasc. Diabetol."},{"key":"86132_CR13","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/1475-2840-11-78","volume":"11","author":"M Mazurek","year":"2012","unstructured":"Mazurek, M. et al. The prognostic value of different glucose abnormalities in patients with acute myocardial infarction treated invasively. Cardiovasc. Diabetol. 11, 78 (2012).","journal-title":"Cardiovasc. Diabetol."},{"issue":"5","key":"86132_CR14","first-page":"734","volume":"124","author":"JL Liang","year":"2011","unstructured":"Liang, J. L. et al. Effect of impaired glucose tolerance on cardiac dysfunction in a rat model of prediabetes. Chin. Med. J. (Engl) 124(5), 734\u2013739 (2011).","journal-title":"Chin. Med. J. (Engl)"},{"issue":"12","key":"86132_CR15","doi-asserted-by":"publisher","first-page":"2461","DOI":"10.1007\/s00125-018-4729-5","volume":"61","author":"MJ Davies","year":"2018","unstructured":"Davies, M. J. et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 61(12), 2461\u20132498 (2018).","journal-title":"Diabetologia"},{"issue":"4","key":"86132_CR16","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1056\/NEJMoa1603827","volume":"375","author":"SP Marso","year":"2016","unstructured":"Marso, S. P. et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 375(4), 311\u2013322 (2016).","journal-title":"N. Engl. J. Med."},{"issue":"2","key":"86132_CR17","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1007\/s10517-019-04676-w","volume":"168","author":"OV Kornyushin","year":"2019","unstructured":"Kornyushin, O. V. et al. Effects of bariatric surgeries on the size of myocardial infarction and ghrelin level in rats with experimental decompensated type 2 diabetes mellitus. Bull. Exp. Biol. Med. 168(2), 210\u2013213 (2019).","journal-title":"Bull. Exp. Biol. Med."},{"key":"86132_CR18","doi-asserted-by":"publisher","first-page":"8317850","DOI":"10.1155\/2016\/8317850","volume":"2016","author":"VK Bayrasheva","year":"2016","unstructured":"Bayrasheva, V. K. et al. Uninephrectomized high-fat-fed nicotinamide-streptozotocin-induced diabetic rats: a model for the investigation of diabetic nephropathy in type 2 diabetes. J. Diabetes Res. 2016, 8317850. https:\/\/doi.org\/10.1155\/2016\/8317850 (2016).","journal-title":"J. Diabetes Res."},{"issue":"1","key":"86132_CR19","first-page":"51","volume":"4","author":"AO Adeyi","year":"2012","unstructured":"Adeyi, A. O. et al. Rat model of food-induced non-obese-type 2 diabetes mellitus: comparative pathophysiology and histopathology. Int. J. Physiol. Pathophysiol. Pharmacol. 4(1), 51\u201358 (2012).","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol."},{"key":"86132_CR20","doi-asserted-by":"publisher","first-page":"704045","DOI":"10.1155\/2008\/704045","volume":"2008","author":"M Zhang","year":"2008","unstructured":"Zhang, M., Lv, X. Y., Li, J., Xu, Z. G. & Chen, L. The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Exp. Diabetes Res. 2008, 704045. https:\/\/doi.org\/10.1155\/2008\/704045 (2008).","journal-title":"Exp. Diabetes Res."},{"issue":"6","key":"86132_CR21","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/S0254-6272(17)30013-4","volume":"36","author":"B Cao","year":"2016","unstructured":"Cao, B. et al. Effect on glycemia in rats with type 2 diabetes induced by streptozotocin: low-frequency electro-pulse needling stimulated Weiwanxiashu (EX-B 3) and Zusanli (ST 36). J. Tradit. Chin. Med. 36(6), 768\u2013778 (2016).","journal-title":"J. Tradit. Chin. Med."},{"key":"86132_CR22","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/1749-8090-8-60","volume":"8","author":"SM Minasian","year":"2013","unstructured":"Minasian, S. M., Galagudza, M. M., Dmitriev, Y. V., Kurapeev, D. I. & Vlasov, T. D. Myocardial protection against global ischemia with Krebs-Henseleit buffer-based cardioplegic solution. J. Cardiothorac. Surg. 8, 60 (2013).","journal-title":"J. Cardiothorac. Surg."},{"issue":"1","key":"86132_CR23","doi-asserted-by":"publisher","first-page":"e000090","DOI":"10.1136\/bmjdrc-2015-000090","volume":"3","author":"CP Lexis","year":"2015","unstructured":"Lexis, C. P. et al. The effect of metformin on cardiovascular risk profile in patients without diabetes presenting with acute myocardial infarction: data from the Glycometabolic Intervention as adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) trial. B.M.J. Open Diabetes Res. Care 3(1), e000090. https:\/\/doi.org\/10.1136\/bmjdrc-2015-000090 (2015).","journal-title":"B.M.J. Open Diabetes Res. Care"},{"issue":"10","key":"86132_CR24","doi-asserted-by":"publisher","first-page":"1946","DOI":"10.2337\/dc18-2356","volume":"42","author":"C Sardu","year":"2019","unstructured":"Sardu, C. et al. Effects of metformin therapy on coronary endothelial dysfunction in patients with prediabetes with stable angina and nonobstructive coronary artery stenosis: the CODYCE multicenter prospective study. Diabetes Care 42(10), 1946\u20131955 (2019).","journal-title":"Diabetes Care"},{"issue":"2","key":"86132_CR25","doi-asserted-by":"publisher","first-page":"H459","DOI":"10.1152\/ajpheart.00054.2011","volume":"301","author":"M Yin","year":"2011","unstructured":"Yin, M. et al. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure. Am. J. Physiol. Heart. Circ. Physiol. 301(2), H459\u2013H468 (2011).","journal-title":"Am. J. Physiol. Heart. Circ. Physiol."},{"issue":"9","key":"86132_CR26","first-page":"8865","volume":"11","author":"L Chen","year":"2018","unstructured":"Chen, L., Zhou, R., Xu, Z. & You, L. Effect of metformin on cardiac function in patients with STEMI: a systematic review and meta-analysis. Int. J. Clin. Exp. Med. 11(9), 8865\u20138872 (2018).","journal-title":"Int. J. Clin. Exp. Med."},{"issue":"6","key":"86132_CR27","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1016\/S1734-1140(12)70945-3","volume":"64","author":"H Soraya","year":"2012","unstructured":"Soraya, H., Khorrami, A., Garjani, A., Maleki-Dizaji, N. & Garjani, A. Acute treatment with metformin improves cardiac function following isoproterenol induced myocardial infarction in rats. Pharmacol. Rep. 64(6), 1476\u20131484 (2012).","journal-title":"Pharmacol. Rep."},{"key":"86132_CR28","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1530\/EJE-10-0624","volume":"163","author":"C Andersson","year":"2010","unstructured":"Andersson, C. et al. Metformin is associated with improved left ventricular diastolic function measured by tissue Doppler imaging in patients with diabetes. Eur. J. Endocrinol. 163, 593\u2013599 (2010).","journal-title":"Eur. J. Endocrinol."},{"issue":"1","key":"86132_CR29","first-page":"81","volume":"24","author":"AV Simanenkova","year":"2018","unstructured":"Simanenkova, A. V., Makarova, M. N., Butomo, M. I., Vlasov, T. D. & Shlyakhto, E. V. Endothelial protective effect of liraglutide in type 2 diabetes mellitus. Arterial Hypertens. 24(1), 81\u201392 (2018).","journal-title":"Arterial Hypertens."},{"issue":"Pt3","key":"86132_CR30","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1042\/bj3480607","volume":"348","author":"MR Owen","year":"2000","unstructured":"Owen, M. R., Doran, E. & Halestrap, A. P. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem. J. 348(Pt3), 607\u2013614 (2000).","journal-title":"Biochem. J."},{"key":"86132_CR31","doi-asserted-by":"publisher","first-page":"907496","DOI":"10.1155\/2011\/907496","volume":"2011","author":"E Kravchuk","year":"2011","unstructured":"Kravchuk, E., Grineva, E., Bairamov, A., Galagudza, M. & Vlasov, T. The effect of metformin on the myocardial tolerance to ischemia-reperfusion injury in the rat model of diabetes mellitus type II. Exp. Diabetes Res. 2011, 907496. https:\/\/doi.org\/10.1155\/2011\/907496 (2011).","journal-title":"Exp. Diabetes Res."},{"issue":"3","key":"86132_CR32","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1161\/01.RES.0000256090.42690.05","volume":"100","author":"MC Towler","year":"2007","unstructured":"Towler, M. C. & Hardie, D. G. AMP-activated protein kinase in metabolic control and insulin signaling. Circ. Res. 100(3), 328\u2013341 (2007).","journal-title":"Circ. Res."},{"issue":"7","key":"86132_CR33","doi-asserted-by":"publisher","first-page":"H749","DOI":"10.1152\/ajpheart.00414.2014","volume":"308","author":"G Barreto-Torres","year":"2015","unstructured":"Barreto-Torres, G. et al. The beneficial effects of AMP kinase activation against oxidative stress are associated with prevention of PPAR\u03b1-cyclophilin D interaction in cardiomyocytes. Am. J. Physiol. Heart Circ. Physiol. 308(7), H749-758 (2015).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"issue":"6","key":"86132_CR34","doi-asserted-by":"publisher","first-page":"7694","DOI":"10.3390\/ijms13067694","volume":"13","author":"G Barreto-Torres","year":"2012","unstructured":"Barreto-Torres, G., Parodi-Rull\u00e1n, R. & Javadov, S. The role of PPAR\u03b1 in metformin-induced attenuation of mitochondrial dysfunction in acute cardiac ischemia\/reperfusion in rats. Int. J. Mol. Sci. 13(6), 7694\u20137709 (2012).","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"86132_CR35","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s12933-019-0857-6","volume":"18","author":"MB Bizino","year":"2019","unstructured":"Bizino, M. B. et al. Effect of liraglutide on cardiac function in patients with type 2 diabetes mellitus: randomized placebo-controlled trial. Cardiovasc. Diabetol. 18(1), 55 (2019).","journal-title":"Cardiovasc. Diabetol."},{"issue":"7","key":"86132_CR36","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.2337\/dc19-2251","volume":"43","author":"JB Buse","year":"2020","unstructured":"Buse, J. B. et al. Cardiovascular risk reduction with liraglutide: an exploratory mediation analysis of the LEADER trial. Diabetes Care 43(7), 1546\u20131552 (2020).","journal-title":"Diabetes Care"},{"key":"86132_CR37","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1016\/S0140-6736(17)30069-7","volume":"389","author":"CW Roux","year":"2017","unstructured":"Roux, C. W. et al. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet 389, 1399\u20131409 (2017).","journal-title":"Lancet"},{"issue":"4","key":"86132_CR38","doi-asserted-by":"publisher","first-page":"975","DOI":"10.2337\/db08-1193","volume":"58","author":"MH Noyan-Ashraf","year":"2009","unstructured":"Noyan-Ashraf, M. H. et al. GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice. Diabetes 58(4), 975\u2013983 (2009).","journal-title":"Diabetes"},{"issue":"14","key":"86132_CR39","first-page":"4648","volume":"22","author":"DD Huang","year":"2018","unstructured":"Huang, D. D., Huang, H. F., Yang, Q. & Chen, X. Q. Liraglutide improves myocardial fibrosis after myocardial infarction through inhibition of CTGF by activating cAMP in mice. Eur. Rev. Med. Pharmacol. Sci. 22(14), 4648\u20134656 (2018).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"86132_CR40","doi-asserted-by":"publisher","first-page":"E640","DOI":"10.1152\/ajpendo.00205.2016","volume":"311","author":"W Chai","year":"2016","unstructured":"Chai, W., Fu, Z., Aylor, K. W., Barrett, E. J. & Liu, Z. Liraglutide prevents microvascular insulin resistance and preserves muscle capillary density in high-fat diet-fed rats. Am. J. Physiol. Endocrinol. Metab. 311, E640\u2013E648 (2016).","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"86132_CR41","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20180059","author":"Q Zhang","year":"2018","unstructured":"Zhang, Q. et al. Liraglutide protects cardiac function in diabetic rats through the PPAR\u03b1 pathway. Biosci. Rep. https:\/\/doi.org\/10.1042\/BSR20180059 (2018)."},{"issue":"18","key":"86132_CR42","doi-asserted-by":"publisher","first-page":"2340","DOI":"10.1161\/CIRCULATIONAHA.107.739938","volume":"117","author":"K Ban","year":"2008","unstructured":"Ban, K. et al. Cardioprotective and vasodilatory actions of glucagon-like peptide-1 receptor are mediated through both glucagon-like peptide-1 receptor-dependent and -independent pathways. Circulation 117(18), 2340\u20132350 (2008).","journal-title":"Circulation"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-86132-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-86132-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-86132-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T05:38:32Z","timestamp":1670045912000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-86132-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,23]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["86132"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-86132-2","relation":{"references":[{"id-type":"uri","id":"","asserted-by":"subject"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,23]]},"assertion":[{"value":"14 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2021","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":"6700"}}