{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:14:15Z","timestamp":1785327255034,"version":"3.55.0"},"reference-count":45,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T00:00:00Z","timestamp":1560988800000},"content-version":"vor","delay-in-days":41,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30-DK-036836"],"award-info":[{"award-number":["P30-DK-036836"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["UL1-RR-025758-03"],"award-info":[{"award-number":["UL1-RR-025758-03"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["T32-DK-007260"],"award-info":[{"award-number":["T32-DK-007260"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008664","name":"JDRF","doi-asserted-by":"publisher","award":["17-2013-310"],"award-info":[{"award-number":["17-2013-310"]}],"id":[{"id":"10.13039\/100008664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:sec><jats:title>OBJECTIVE<\/jats:title><jats:p>Elevated glycolytic enzymes in renal glomeruli correlated with preservation of renal function in the Medalist Study, individuals with \u226550 years of type 1 diabetes. Specifically, pyruvate kinase M2 (PKM2) activation protected insulin-deficient diabetic mice from hyperglycemia-induced glomerular pathology. This study aims to extend these findings in a separate cohort of individuals with type 1 and type 2 diabetes and discover new circulatory biomarkers for renal protection through proteomics and metabolomics of Medalists\u2019 plasma. We hypothesize that increased glycolytic flux and improved mitochondrial biogenesis will halt the progression of diabetic nephropathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESEARCH DESIGN AND METHODS<\/jats:title><jats:p>Immunoblots analyzed selected glycolytic and mitochondrial enzymes in postmortem glomeruli of non-Medalists with type 1 diabetes (n = 15), type 2 diabetes (n = 19), and no diabetes (n = 5). Plasma proteomic (SOMAscan) (n = 180) and metabolomic screens (n = 214) of Medalists with and without stage 3b chronic kidney disease (CKD) were conducted and significant markers validated by ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Glycolytic (PKM1, PKM2, and ENO1) and mitochondrial (MTCO2) enzymes were significantly elevated in glomeruli of CKD\u2212 versus CKD+ individuals with type 2 diabetes. Medalists\u2019 plasma PKM2 correlated with estimated glomerular filtration rate (r2 = 0.077; P = 0.0002). Several glucose and mitochondrial enzymes in circulation were upregulated with corresponding downregulation of toxic metabolites in CKD-protected Medalists. Amyloid precursor protein was also significantly upregulated, tumor necrosis factor receptors downregulated, and both confirmed by ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Elevation of enzymes involved in the metabolism of intracellular free glucose and its metabolites in renal glomeruli is connected to preserving kidney function in both type 1 and type 2 diabetes. The renal profile of elevated glycolytic enzymes and reduced toxic glucose metabolites is reflected in the circulation, supporting their use as biomarkers for endogenous renal protective factors in people with diabetes.<\/jats:p><\/jats:sec>","DOI":"10.2337\/dc18-2585","type":"journal-article","created":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T21:05:46Z","timestamp":1557522346000},"page":"1263-1273","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":90,"title":["Characterization of Glycolytic Enzymes and Pyruvate Kinase M2 in Type 1 and 2 Diabetic Nephropathy"],"prefix":"10.2337","volume":"42","author":[{"given":"Daniel","family":"Gordin","sequence":"first","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"},{"name":"Folkh\u00e4lsan Research Center, University of Helsinki, Helsinki, Finland"},{"name":"Abdominal Center Nephrology, Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3685-4572","authenticated-orcid":false,"given":"Hetal","family":"Shah","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Shinjo","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"St-Louis","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weier","family":"Qi","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"},{"name":"Translational Research and Early Clinical Development, Cardiovascular and Metabolic Research, AstraZeneca, M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoungmin","family":"Park","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha M.","family":"Paniagua","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Pober","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Hsien","family":"Wu","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Bahnam","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan J.","family":"Brissett","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liane J.","family":"Tinsley","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Dreyfuss","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Pan","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Dong","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2371-595X","authenticated-orcid":false,"given":"Monika A.","family":"Niewczas","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Amenta","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Sadowski","sequence":"additional","affiliation":[{"name":"Sanofi Deutschland GmbH, Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimo","family":"Kannt","sequence":"additional","affiliation":[{"name":"Sanofi Deutschland GmbH, Frankfurt am Main, Germany"},{"name":"Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4172-5537","authenticated-orcid":false,"given":"Hillary A.","family":"Keenan","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"},{"name":"Sanofi-Genzyme, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0335-5881","authenticated-orcid":false,"given":"George L.","family":"King","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2019,5,10]]},"reference":[{"key":"2022031300522950200_B1","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1056\/NEJMoa1310799","article-title":"Changes in diabetes-related complications in the United States, 1990-2010","volume":"370","author":"Gregg","year":"2014","journal-title":"N Engl J Med"},{"key":"2022031300522950200_B2","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.2337\/db08-1543","article-title":"The presence and severity of chronic kidney disease predicts all-cause mortality in type 1 diabetes","volume":"58","author":"Groop","year":"2009","journal-title":"Diabetes"},{"key":"2022031300522950200_B3","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1007\/s00125-010-1860-3","article-title":"In the absence of renal disease, 20 year mortality risk in type 1 diabetes is comparable to that of the general population: a report from the Pittsburgh Epidemiology of Diabetes Complications Study","volume":"53","author":"Orchard","year":"2010","journal-title":"Diabetologia"},{"key":"2022031300522950200_B4","doi-asserted-by":"crossref","first-page":"5141","DOI":"10.1073\/pnas.86.13.5141","article-title":"Activation of protein kinase C by elevation of glucose concentration: proposal for a mechanism in the development of diabetic vascular complications","volume":"86","author":"Lee","year":"1989","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022031300522950200_B5","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1046\/j.1523-1755.2000.07702.x","article-title":"Aldose reductase and the role of the polyol pathway in diabetic nephropathy","volume":"77","author":"Dunlop","year":"2000","journal-title":"Kidney Int Suppl"},{"key":"2022031300522950200_B6","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1056\/NEJM198703053161007","article-title":"Sorbitol, phosphoinositides, and sodium-potassium-ATPase in the pathogenesis of diabetic complications","volume":"316","author":"Greene","year":"1987","journal-title":"N Engl J Med"},{"key":"2022031300522950200_B7","doi-asserted-by":"crossref","first-page":"291","DOI":"10.2337\/db13-0316","article-title":"Knockdown of glyoxalase 1 mimics diabetic nephropathy in nondiabetic mice","volume":"63","author":"Giacco","year":"2014","journal-title":"Diabetes"},{"key":"2022031300522950200_B8","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1681\/ASN.2009060593","article-title":"Avosentan for overt diabetic nephropathy","volume":"21","author":"Mann","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"2022031300522950200_B9","doi-asserted-by":"crossref","first-page":"169","DOI":"10.2337\/diab.43.2.169","article-title":"The aldose reductase controversy","volume":"43","author":"Frank","year":"1994","journal-title":"Diabetes"},{"key":"2022031300522950200_B10","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1056\/NEJMoa1306033","article-title":"Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease","volume":"369","author":"de Zeeuw","year":"2013","journal-title":"N Engl J Med"},{"key":"2022031300522950200_B11","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.2337\/dc06-2222","article-title":"Clinical factors associated with resistance to microvascular complications in diabetic patients of extreme disease duration: the 50-year Medalist Study","volume":"30","author":"Keenan","year":"2007","journal-title":"Diabetes Care"},{"key":"2022031300522950200_B12","doi-asserted-by":"crossref","first-page":"815","DOI":"10.2337\/dc17-2250","article-title":"Differential association of microvascular attributions with cardiovascular disease in patients with long duration of type 1 diabetes","volume":"41","author":"Gordin","year":"2018","journal-title":"Diabetes Care"},{"key":"2022031300522950200_B13","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/nm.4328","article-title":"Pyruvate kinase M2 activation may protect against the progression of diabetic glomerular pathology and mitochondrial dysfunction","volume":"23","author":"Qi","year":"2017","journal-title":"Nat Med"},{"key":"2022031300522950200_B14","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.1210\/jc.2017-00589","article-title":"Association of glycemic control with reduced risk for large-vessel disease after more than 50 years of type 1 diabetes","volume":"102","author":"Tinsley","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031300522950200_B15","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1161\/CIRCULATIONAHA.116.021803","article-title":"Aptamer-based proteomic profiling reveals novel candidate biomarkers and pathways in cardiovascular disease","volume":"134","author":"Ngo","year":"2016","journal-title":"Circulation"},{"key":"2022031300522950200_B16","doi-asserted-by":"crossref","first-page":"2931","DOI":"10.1073\/pnas.1115813109","article-title":"Skeletal muscle transcriptional coactivator PGC-1\u03b1 mediates mitochondrial, but not metabolic, changes during calorie restriction","volume":"109","author":"Finley","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022031300522950200_B17","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1126\/science.1218595","article-title":"Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation","volume":"336","author":"Jain","year":"2012","journal-title":"Science"},{"key":"2022031300522950200_B18","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1681\/ASN.2011060627","article-title":"Circulating TNF receptors 1 and 2 predict ESRD in type 2 diabetes","volume":"23","author":"Niewczas","year":"2012","journal-title":"J Am Soc Nephrol"},{"key":"2022031300522950200_B19","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2022031300522950200_B20","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc B"},{"key":"2022031300522950200_B21","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1093\/bioinformatics\/btq401","article-title":"ROAST: rotation gene set tests for complex microarray experiments","volume":"26","author":"Wu","year":"2010","journal-title":"Bioinformatics"},{"key":"2022031300522950200_B22","doi-asserted-by":"crossref","first-page":"D685","DOI":"10.1093\/nar\/gkq1039","article-title":"Pathway Commons, a web resource for biological pathway data","volume":"39","author":"Cerami","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"2022031300522950200_B23","first-page":"1","article-title":"The igraph software package for complex network research","volume":"1695","author":"Csardi","year":"2006","journal-title":"InterJournal Complex Syst"},{"key":"2022031300522950200_B24","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1172\/JCI72271","article-title":"Molecular mechanisms of diabetic kidney disease","volume":"124","author":"Reidy","year":"2014","journal-title":"J Clin Invest"},{"key":"2022031300522950200_B25","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41581-018-0078-3","article-title":"The Klotho proteins in health and disease","volume":"15","author":"Kuro-O","year":"2019","journal-title":"Nat Rev Nephrol"},{"key":"2022031300522950200_B26","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1159\/000447954","article-title":"Metabolomics in diabetic kidney disease: unraveling the biochemistry of a silent killer","volume":"44","author":"Darshi","year":"2016","journal-title":"Am J Nephrol"},{"key":"2022031300522950200_B27","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1172\/JCI118754","article-title":"Intracellular lactate- and pyruvate-interconversion rates are increased in muscle tissue of non-insulin-dependent diabetic individuals","volume":"98","author":"Avogaro","year":"1996","journal-title":"J Clin Invest"},{"key":"2022031300522950200_B28","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1007\/s00125-012-2469-5","article-title":"Coenzyme Q10 prevents GDP-sensitive mitochondrial uncoupling, glomerular hyperfiltration and proteinuria in kidneys from db\/db mice as a model of type 2 diabetes","volume":"55","author":"Persson","year":"2012","journal-title":"Diabetologia"},{"key":"2022031300522950200_B29","doi-asserted-by":"crossref","first-page":"338","DOI":"10.3389\/fphys.2012.00338","article-title":"Pravastatin-induced improvement in coronary reactivity and circulating ATP and ADP levels in young adults with type 1 diabetes","volume":"3","author":"Kiviniemi","year":"2012","journal-title":"Front Physiol"},{"key":"2022031300522950200_B30","doi-asserted-by":"crossref","first-page":"E1067","DOI":"10.1073\/pnas.1417197112","article-title":"L-cysteine reversibly inhibits glucose-induced biphasic insulin secretion and ATP production by inactivating PKM2","volume":"112","author":"Nakatsu","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022031300522950200_B31","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.cmet.2010.04.001","article-title":"Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation","volume":"11","author":"Hawley","year":"2010","journal-title":"Cell Metab"},{"key":"2022031300522950200_B32","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","volume":"324","author":"Vander Heiden","year":"2009","journal-title":"Science"},{"key":"2022031300522950200_B33","doi-asserted-by":"crossref","first-page":"3154","DOI":"10.4161\/cc.26182","article-title":"Nuclear PKM2 regulates the Warburg effect","volume":"12","author":"Yang","year":"2013","journal-title":"Cell Cycle"},{"key":"2022031300522950200_B34","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.cmet.2015.01.017","article-title":"Pyruvate kinase M2 regulates hif-1\u03b1 activity and IL-1\u03b2 induction and is a critical determinant of the Warburg effect in LPS-activated macrophages","volume":"21","author":"Palsson-McDermott","year":"2015","journal-title":"Cell Metab"},{"key":"2022031300522950200_B35","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.3945\/ajcn.2010.29885","article-title":"Specific metabolic rates of major organs and tissues across adulthood: evaluation by mechanistic model of resting energy expenditure","volume":"92","author":"Wang","year":"2010","journal-title":"Am J Clin Nutr"},{"key":"2022031300522950200_B36","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.2174\/1389450116666150727114410","article-title":"Tapping into mitochondria to find novel targets for diabetes complications","volume":"17","author":"Flemming","year":"2016","journal-title":"Curr Drug Targets"},{"key":"2022031300522950200_B37","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1016\/j.metabol.2012.04.004","article-title":"VEGF and angiopoietins in diabetic glomerulopathy: how far for a new treatment","volume":"61","author":"Dei Cas","year":"2012","journal-title":"Metabolism"},{"key":"2022031300522950200_B38","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nrn.2017.29","article-title":"Not just amyloid: physiological functions of the amyloid precursor protein family","volume":"18","author":"M\u00fcller","year":"2017","journal-title":"Nat Rev Neurosci"},{"key":"2022031300522950200_B39","first-page":"20","article-title":"Expression and processing of amyloid precursor protein in vascular endothelium","volume":"32","author":"d\u2019Uscio","year":"2017","journal-title":"Physiology (Bethesda)"},{"key":"2022031300522950200_B40","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s00401-010-0762-2","article-title":"APP involvement in retinogenesis of mice","volume":"121","author":"Dinet","year":"2011","journal-title":"Acta Neuropathol"},{"key":"2022031300522950200_B41","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1126\/science.2111585","article-title":"Platelet coagulation factor XIa-inhibitor, a form of Alzheimer amyloid precursor protein","volume":"248","author":"Smith","year":"1990","journal-title":"Science"},{"key":"2022031300522950200_B42","doi-asserted-by":"crossref","first-page":"5189","DOI":"10.1038\/onc.2017.140","article-title":"Thrombospondin-4 mediates TGF-\u03b2-induced angiogenesis","volume":"36","author":"Muppala","year":"2017","journal-title":"Oncogene"},{"key":"2022031300522950200_B43","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1161\/01.CIR.0000089085.76320.4E","article-title":"Thrombospondin-4 and its variants: expression and differential effects on endothelial cells","volume":"108","author":"Stenina","year":"2003","journal-title":"Circulation"},{"key":"2022031300522950200_B44","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/cns.12503","article-title":"Hyperglycemia increases the production of amyloid beta-peptide leading to decreased endothelial tight junction","volume":"22","author":"Chao","year":"2016","journal-title":"CNS Neurosci Ther"},{"key":"2022031300522950200_B45","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/1056-8727(95)80015-7","article-title":"Extracellular matrix and its interactions in the diabetic kidney: a molecular biological approach","volume":"9","author":"Gilbert","year":"1995","journal-title":"J Diabetes Complications"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/care.diabetesjournals.org\/syndication\/doi\/10.2337\/dc18-2585","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/42\/7\/1263\/530292\/dc182585.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/42\/7\/1263\/530292\/dc182585.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T22:37:13Z","timestamp":1721255833000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/42\/7\/1263\/36231\/Characterization-of-Glycolytic-Enzymes-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,10]]},"references-count":45,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,5,10]]},"published-print":{"date-parts":[[2019,7,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc18-2585","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,10]]}}}