{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:35:51Z","timestamp":1787063751894,"version":"build-2736575974"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"PPP Allowance made available by Health\u223cHolland, Top Sector Life Sciences & Health\/ JPI HDHL and of the ERA-NET Cofund HDHL-INTIMIC","award":["GA N\u00b0727565"],"award-info":[{"award-number":["GA N\u00b0727565"]}]},{"name":"PPP Allowance made available by Health\u223cHolland, Top Sector Life Sciences & Health\/ JPI HDHL and of the ERA-NET Cofund HDHL-INTIMIC","award":["GA N\u00b0727565"],"award-info":[{"award-number":["GA N\u00b0727565"]}]},{"DOI":"10.13039\/501100003092","name":"Dutch Diabetes Research Foundation","doi-asserted-by":"crossref","award":["No. 2021.81.005"],"award-info":[{"award-number":["No. 2021.81.005"]}],"id":[{"id":"10.13039\/501100003092","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Dutch Organisation for knowledge and innovation in health, healthcare and well-being","award":["01142042310002"],"award-info":[{"award-number":["01142042310002"]}]},{"name":"Dutch Organisation for knowledge and innovation in health, healthcare and well-being","award":["01142042310002"],"award-info":[{"award-number":["01142042310002"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-90661-5","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T04:58:11Z","timestamp":1739941091000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Modelling the effects of elevated methylglyoxal levels on vascular and metabolic complications"],"prefix":"10.1038","volume":"15","author":[{"given":"Philippe","family":"Vangrieken","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean L. J. M.","family":"Scheijen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M. H.","family":"Schiffers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjo P. H.","family":"van de Waarenburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Foulquier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casper C. G.","family":"Schalkwijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"90661_CR1","doi-asserted-by":"publisher","unstructured":"Schalkwijk, C. G. & Stehouwer, C. D. A. Methylglyoxal, a highly reactive dicarbonyl compound, in diabetes, its vascular complications, and other age-related diseases. Physiol. Rev. 100, 407\u2013461.  https:\/\/doi.org\/10.1152\/physrev.00001.2019 (2020).","DOI":"10.1152\/physrev.00001.2019"},{"key":"90661_CR2","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1042\/CS20140683","volume":"128","author":"DE Maessen","year":"2015","unstructured":"Maessen, D. E., Stehouwer, C. D. & Schalkwijk, C. G. The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases. Clin. Sci. (Lond.). 128, 839\u2013861. https:\/\/doi.org\/10.1042\/CS20140683 (2015).","journal-title":"Clin. Sci. (Lond.)"},{"key":"90661_CR3","doi-asserted-by":"publisher","first-page":"7071","DOI":"10.1021\/jf301306g","volume":"60","author":"J Degen","year":"2012","unstructured":"Degen, J., Hellwig, M. & Henle, T. 1,2-dicarbonyl compounds in commonly consumed foods. J. Agric. Food Chem. 60, 7071\u20137079. https:\/\/doi.org\/10.1021\/jf301306g (2012).","journal-title":"J. Agric. Food Chem."},{"key":"90661_CR4","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1016\/j.foodchem.2015.06.049","volume":"190","author":"JL Scheijen","year":"2016","unstructured":"Scheijen, J. L. et al. Analysis of advanced glycation endproducts in selected food items by ultra-performance liquid chromatography tandem mass spectrometry: presentation of a dietary AGE database. Food Chem. 190, 1145\u20131150 (2016).","journal-title":"Food Chem."},{"key":"90661_CR5","doi-asserted-by":"publisher","first-page":"15724","DOI":"10.3390\/ijms140815724","volume":"14","author":"O Brouwers","year":"2013","unstructured":"Brouwers, O. et al. Mild oxidative damage in the diabetic rat heart is attenuated by glyoxalase-1 overexpression. Int. J. Mol. Sci. 14, 15724\u201315739 (2013).","journal-title":"Int. J. Mol. Sci."},{"key":"90661_CR6","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1074\/jbc.M110.144097","volume":"286","author":"O Brouwers","year":"2011","unstructured":"Brouwers, O. et al. Overexpression of glyoxalase-I reduces hyperglycemia-induced levels of advanced glycation end products and oxidative stress in diabetic rats. J. Biol. Chem. 286, 1374\u20131380 (2011).","journal-title":"J. Biol. Chem."},{"key":"90661_CR7","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.tem.2022.11.004","volume":"34","author":"CG Schalkwijk","year":"2023","unstructured":"Schalkwijk, C. G., Micali, L. R. & Wouters, K. Advanced glycation endproducts in diabetes-related macrovascular complications: focus on methylglyoxal. Trends Endocrinol. Metab.. 34, 49\u201360 (2023).","journal-title":"Trends Endocrinol. Metab."},{"key":"90661_CR8","unstructured":"Rabbani, N. & Thornalley, P. J. (Portland Press Ltd., 2008)."},{"key":"90661_CR9","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1096\/fj.05-5478fje","volume":"20","author":"X Jia","year":"2006","unstructured":"Jia, X. et al. Structural and functional changes in human insulin induced by methylglyoxal. FASEB J. 20, 1555\u20131557 (2006).","journal-title":"FASEB J."},{"key":"90661_CR10","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1007\/s00125-014-3243-7","volume":"57","author":"C Nigro","year":"2014","unstructured":"Nigro, C. et al. Methylglyoxal impairs endothelial insulin sensitivity both in vitro and in vivo. Diabetologia 57, 1485\u20131494 (2014).","journal-title":"Diabetologia"},{"key":"90661_CR11","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1210\/jc.2007-1817","volume":"93","author":"SY Goh","year":"2008","unstructured":"Goh, S. Y. & Cooper, M. E. Clinical review: the role of advanced glycation end products in progression and complications of diabetes. J. Clin. Endocrinol. Metab. 93, 1143\u20131152. https:\/\/doi.org\/10.1210\/jc.2007-1817 (2008).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"90661_CR12","doi-asserted-by":"publisher","first-page":"2941","DOI":"10.1007\/s00125-011-2280-8","volume":"54","author":"F Fiory","year":"2011","unstructured":"Fiory, F. et al. Methylglyoxal impairs insulin signalling and insulin action on glucose-induced insulin secretion in the pancreatic beta cell line INS-1E. Diabetologia 54, 2941\u20132952 (2011).","journal-title":"Diabetologia"},{"key":"90661_CR13","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1007\/s00726-010-0783-0","volume":"42","author":"N Rabbani","year":"2012","unstructured":"Rabbani, N. & Thornalley, P. J. Methylglyoxal, glyoxalase 1 and the dicarbonyl proteome. Amino Acids. 42, 1133\u20131142. https:\/\/doi.org\/10.1007\/s00726-010-0783-0 (2012).","journal-title":"Amino Acids"},{"key":"90661_CR14","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1007\/s11906-009-0010-0","volume":"11","author":"IH Schulman","year":"2009","unstructured":"Schulman, I. H. & Zhou, M. S. Vascular insulin resistance: a potential link between cardiovascular and metabolic diseases. Curr. Hypertens. Rep. 11, 48\u201355 (2009).","journal-title":"Curr. Hypertens. Rep."},{"key":"90661_CR15","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s11010-007-9535-1","volume":"305","author":"Y Han","year":"2007","unstructured":"Han, Y. et al. Plasma methylglyoxal and glyoxal are elevated and related to early membrane alteration in young, complication-free patients with type 1 diabetes. Mol. Cell. Biochem. 305, 123\u2013131 (2007).","journal-title":"Mol. Cell. Biochem."},{"key":"90661_CR16","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.clinbiochem.2010.11.004","volume":"44","author":"J Lu","year":"2011","unstructured":"Lu, J. et al. Increased plasma methylglyoxal level, inflammation, and vascular endothelial dysfunction in diabetic nephropathy. Clin. Biochem. 44, 307\u2013311 (2011).","journal-title":"Clin. Biochem."},{"key":"90661_CR17","doi-asserted-by":"crossref","unstructured":"Daugherty, A., Rateri, D., Hong, L. & Balakrishnan, A. Measuring blood pressure in mice using volume pressure recording, a tail-cuff method. J. Vis. Exp. JoVE (2009).","DOI":"10.3791\/1291-v"},{"key":"90661_CR18","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1515\/cclm-2012-0878","volume":"52","author":"JL Scheijen","year":"2014","unstructured":"Scheijen, J. L. & Schalkwijk, C. G. Quantification of glyoxal, methylglyoxal and 3-deoxyglucosone in blood and plasma by ultra performance liquid chromatography tandem mass spectrometry: evaluation of blood specimen. Clin. Chem. Lab. Med. 52, 85\u201391 (2014).","journal-title":"Clin. Chem. Lab. Med."},{"key":"90661_CR19","doi-asserted-by":"publisher","first-page":"e0221058","DOI":"10.1371\/journal.pone.0221058","volume":"14","author":"RJ Martens","year":"2019","unstructured":"Martens, R. J. et al. Relations of advanced glycation endproducts and dicarbonyls with endothelial dysfunction and low-grade inflammation in individuals with end-stage renal disease in the transition to renal replacement therapy: a cross-sectional observational study. PLoS One. 14, e0221058 (2019).","journal-title":"PLoS One"},{"key":"90661_CR20","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1006\/abio.1993.1229","volume":"211","author":"AC McLellan","year":"1993","unstructured":"McLellan, A. C., Phillips, S. A. & Thornalley, P. J. The assay of SD-lactoylglutathione in biological systems. Anal. Biochem. 211, 37\u201343 (1993).","journal-title":"Anal. Biochem."},{"key":"90661_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/bj3640001","volume":"364","author":"N Ahmed","year":"2002","unstructured":"Ahmed, N., Argirov, O. K., Minhas, H. S., Cordeiro, C. A. & Thornalley, P. J. Assay of advanced glycation endproducts (AGEs): surveying AGEs by chromatographic assay with derivatization by 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate and application to N\u220a-carboxymethyl-lysine-and N\u220a-(1-carboxyethyl) lysine-modified albumin. Biochem. J. 364, 1\u201314 (2002).","journal-title":"Biochem. J."},{"key":"90661_CR22","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1038\/s41440-020-0528-8","volume":"43","author":"P Vangrieken","year":"2020","unstructured":"Vangrieken, P. et al. Placental hypoxia-induced alterations in vascular function, morphology, and endothelial barrier integrity. Hypertens. Res. 43, 1361\u20131374. https:\/\/doi.org\/10.1038\/s41440-020-0528-8 (2020).","journal-title":"Hypertens. Res."},{"key":"90661_CR23","doi-asserted-by":"publisher","first-page":"e64860","DOI":"10.1371\/journal.pone.0064860","volume":"8","author":"M Wang","year":"2013","unstructured":"Wang, M., Li, J., Lim, G. E. & Johnson, J. D. Is dynamic autocrine insulin signaling possible? A mathematical model predicts picomolar concentrations of extracellular monomeric insulin within human pancreatic islets. PLoS One. 8, e64860 (2013).","journal-title":"PLoS One"},{"key":"90661_CR24","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1161\/HYPERTENSIONAHA.123.22633","volume":"81","author":"P Vangrieken","year":"2024","unstructured":"Vangrieken, P. et al. Placental methylglyoxal in preeclampsia: vascular and biomarker implications. Hypertension 81, 1537\u20131549 (2024).","journal-title":"Hypertension"},{"key":"90661_CR25","doi-asserted-by":"publisher","first-page":"2601","DOI":"10.1093\/jn\/nxab176","volume":"151","author":"Y Zhao","year":"2021","unstructured":"Zhao, Y., Tang, Y. & Sang, S. Dietary quercetin reduces plasma and tissue methylglyoxal and advanced glycation end products in healthy mice treated with methylglyoxal. J. Nutr. 151, 2601\u20132609 (2021).","journal-title":"J. Nutr."},{"key":"90661_CR26","doi-asserted-by":"publisher","first-page":"1902","DOI":"10.1017\/S0007114524000503","volume":"131","author":"C Debras","year":"2024","unstructured":"Debras, C. et al. Dietary intake of dicarbonyl compounds and changes in body weight over time in a large cohort of European adults. Br. J. Nutr. 131, 1902\u20131914 (2024).","journal-title":"Br. J. Nutr."},{"key":"90661_CR27","doi-asserted-by":"publisher","first-page":"2282","DOI":"10.2337\/db16-0153","volume":"65","author":"M Xue","year":"2016","unstructured":"Xue, M. et al. Improved glycemic control and vascular function in overweight and obese subjects by glyoxalase 1 inducer formulation. Diabetes 65, 2282\u20132294 (2016).","journal-title":"Diabetes"},{"key":"90661_CR28","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1007\/s00726-010-0783-0","volume":"42","author":"N Rabbani","year":"2012","unstructured":"Rabbani, N. & Thornalley, P. J. Methylglyoxal, glyoxalase 1 and the dicarbonyl proteome. Amino Acids. 42, 1133\u20131142 (2012).","journal-title":"Amino Acids"},{"key":"90661_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/bj2690001","volume":"269","author":"PJ Thornalley","year":"1990","unstructured":"Thornalley, P. J. The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life. Biochem. J. 269, 1\u201311. https:\/\/doi.org\/10.1042\/bj2690001 (1990).","journal-title":"Biochem. J."},{"key":"90661_CR30","unstructured":"Rabbani, N. & Thornalley, P. J. In Seminars in Cell & Developmental Biology. 309\u2013317 (Elsevier)."},{"key":"90661_CR31","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1089\/ars.2017.7424","volume":"30","author":"N Rabbani","year":"2019","unstructured":"Rabbani, N. & Thornalley, P. J. Glyoxalase 1 modulation in obesity and diabetes. Antioxid. Redox. Signal. 30, 354\u2013374 (2019).","journal-title":"Antioxid. Redox. Signal."},{"key":"90661_CR32","doi-asserted-by":"publisher","first-page":"111333","DOI":"10.1016\/j.fct.2020.111333","volume":"141","author":"K Zunkel","year":"2020","unstructured":"Zunkel, K., Simm, A. & Bartling, B. Long-term intake of the reactive metabolite methylglyoxal is not toxic in mice. Food Chem. Toxicol. 141, 111333 (2020).","journal-title":"Food Chem. Toxicol."},{"key":"90661_CR33","doi-asserted-by":"publisher","first-page":"101148","DOI":"10.1016\/j.diabet.2020.02.002","volume":"47","author":"N Hanssen","year":"2021","unstructured":"Hanssen, N. et al. Fasting and post-oral-glucose-load levels of methylglyoxal are associated with microvascular, but not macrovascular, disease in individuals with and without (pre) diabetes: the Maastricht Study. Diabetes Metab. 47, 101148 (2021).","journal-title":"Diabetes Metab."},{"key":"90661_CR34","doi-asserted-by":"publisher","unstructured":"Amezcua-Castillo, E. et al. C-Reactive protein: the quintessential marker of systemic inflammation in coronary artery disease-advancing toward precision medicine. Biomedicines 11 https:\/\/doi.org\/10.3390\/biomedicines11092444 (2023).","DOI":"10.3390\/biomedicines11092444"},{"key":"90661_CR35","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.3389\/fimmu.2017.01058","volume":"8","author":"I Mozos","year":"2017","unstructured":"Mozos, I. et al. Inflammatory markers for arterial stiffness in cardiovascular diseases. Front. Immunol. 8, 1058 (2017).","journal-title":"Front. Immunol."},{"key":"90661_CR36","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1210\/jc.2007-1817","volume":"93","author":"SY Goh","year":"2008","unstructured":"Goh, S. Y. & Cooper, M. E. The role of advanced glycation end products in progression and complications of diabetes. J. Clin. Endocrinol. Metabolism. 93, 1143\u20131152 (2008).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"90661_CR37","doi-asserted-by":"publisher","first-page":"4929","DOI":"10.3390\/nu14224929","volume":"14","author":"M Csongov\u00e1","year":"2022","unstructured":"Csongov\u00e1, M. et al. Association of \u03b1-dicarbonyls and advanced glycation end products with insulin resistance in non-diabetic young subjects: a case-control study. Nutrients 14, 4929 (2022).","journal-title":"Nutrients"},{"key":"90661_CR38","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1254\/jphs.12088FP","volume":"120","author":"M Mukohda","year":"2012","unstructured":"Mukohda, M., Okada, M., Hara, Y. & Yamawaki, H. Methylglyoxal accumulation in arterial walls causes vascular contractile dysfunction in spontaneously hypertensive rats. J. Pharmacol. Sci. 120, 26\u201335 (2012).","journal-title":"J. Pharmacol. Sci."},{"key":"90661_CR39","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1016\/j.hlc.2021.06.527","volume":"30","author":"MM van der Bruggen","year":"2021","unstructured":"van der Bruggen, M. M., Spronck, B., Delhaas, T., Reesink, K. D. & Schalkwijk, C. G. The putative role of methylglyoxal in arterial stiffening: a review. Heart Lung Circ. 30, 1681\u20131693. https:\/\/doi.org\/10.1016\/j.hlc.2021.06.527 (2021).","journal-title":"Heart Lung Circ."},{"key":"90661_CR40","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1093\/ajh\/hpt281","volume":"27","author":"I Dhar","year":"2014","unstructured":"Dhar, I., Dhar, A., Wu, L. & Desai, K. M. Methylglyoxal, a reactive glucose metabolite, increases renin angiotensin aldosterone and blood pressure in male Sprague\u2013Dawley rats. Am. J. Hypertens. 27, 308\u2013316. https:\/\/doi.org\/10.1093\/ajh\/hpt281 (2014).","journal-title":"Am. J. Hypertens."},{"key":"90661_CR41","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-024-04552-3","author":"E Berends","year":"2024","unstructured":"Berends, E. et al. Increased levels of circulating methylglyoxal have no consequence for cerebral microvascular integrity and cognitive function in Young Healthy mice. Mol. Neurobiol. https:\/\/doi.org\/10.1007\/s12035-024-04552-3 (2024).","journal-title":"Mol. Neurobiol."},{"key":"90661_CR42","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1161\/01.CIR.100.8.820","volume":"100","author":"C Cardillo","year":"1999","unstructured":"Cardillo, C. et al. Insulin stimulates both endothelin and nitric oxide activity in the human forearm. Circulation 100, 820\u2013825 (1999).","journal-title":"Circulation"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-90661-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-90661-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-90661-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T04:58:20Z","timestamp":1739941100000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-90661-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,19]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["90661"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-90661-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,19]]},"assertion":[{"value":"6 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6025"}}