{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:43:04Z","timestamp":1791265384274,"version":"4.1.0"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T00:00:00Z","timestamp":1453420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0147634","type":"journal-article","created":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T21:06:13Z","timestamp":1453496773000},"page":"e0147634","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":62,"title":["Improved Muscle Function in Duchenne Muscular Dystrophy through L-Arginine and Metformin: An Investigator-Initiated, Open-Label, Single-Center, Proof-Of-Concept-Study"],"prefix":"10.1371","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct02516085","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Patricia","family":"Hafner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Bonati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beat","family":"Erne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice","family":"Schmid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Rubino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urs","family":"Pohlman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Rutz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Frank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Neuhaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Deuster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Gloor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Bieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Fischmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sinnreich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuri","family":"Gueven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,1,22]]},"reference":[{"issue":"5","key":"ref1","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1093\/oxfordjournals.jbchem.a123276","article-title":"Glycoprotein complex anchoring dystrophin to sarcolemma","volume":"108","author":"M Yoshida","year":"1990","journal-title":"Journal of biochemistry"},{"issue":"6212","key":"ref2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/338259a0","article-title":"Association of dystrophin and an integral membrane glycoprotein","volume":"338","author":"KP Campbell","year":"1989","journal-title":"Nature"},{"issue":"5","key":"ref3","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/35072063","article-title":"The genetics and pathology of oxidative phosphorylation","volume":"2","author":"J Smeitink","year":"2001","journal-title":"Nature reviews Genetics"},{"issue":"9","key":"ref4","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1212\/WNL.35.9.1396","article-title":"Muscle mitochondria from patients with Duchenne muscular dystrophy have a normal beta oxidation, but an impaired oxidative phosphorylation","volume":"35","author":"HR Scholte","year":"1985","journal-title":"Neurology"},{"issue":"2","key":"ref5","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0022-510X(93)90326-T","article-title":"Cellular energetics of dystrophic muscle","volume":"116","author":"GJ Kemp","year":"1993","journal-title":"Journal of the neurological sciences"},{"issue":"1\u20132","key":"ref6","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1023\/A:1006880529195","article-title":"High resolution respirometry of permeabilized skeletal muscle fibers in the diagnosis of neuromuscular disorders","volume":"174","author":"W Sperl","year":"1997","journal-title":"Molecular and cellular biochemistry"},{"issue":"1\u20132","key":"ref7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1023\/A:1006868130002","article-title":"Impaired mitochondrial oxidative phosphorylation in skeletal muscle of the dystrophin-deficient mdx mouse","volume":"183","author":"AV Kuznetsov","year":"1998","journal-title":"Molecular and cellular biochemistry"},{"issue":"2\u20133","key":"ref8","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/S0005-2728(01)00172-4","article-title":"Lack of dystrophin is associated with altered integration of the mitochondria and ATPases in slow-twitch muscle cells of MDX mice","volume":"1505","author":"U Braun","year":"2001","journal-title":"Biochimica et biophysica acta"},{"issue":"4","key":"ref9","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/nm1736","article-title":"Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy","volume":"14","author":"DP Millay","year":"2008","journal-title":"Nature medicine"},{"issue":"1","key":"ref10","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1203\/00006450-199607000-00006","article-title":"Resting energy expenditure and energy substrate utilization in children with Duchenne muscular dystrophy","volume":"40","author":"R Hankard","year":"1996","journal-title":"Pediatric research"},{"issue":"8","key":"ref11","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1007\/s00256-011-1301-5","article-title":"Muscle fat-fraction and mapping in Duchenne muscular dystrophy: evaluation of disease distribution and correlation with clinical assessments. Preliminary experience","volume":"41","author":"M Gaeta","year":"2012","journal-title":"Skeletal radiology"},{"issue":"4","key":"ref12","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1002\/mus.23879","article-title":"Magnetic resonance imaging in Duchenne muscular dystrophy: longitudinal assessment of natural history over 18 months","volume":"48","author":"KG Hollingsworth","year":"2013","journal-title":"Muscle & nerve"},{"issue":"5","key":"ref13","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/0092-8674(95)90471-9","article-title":"Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy","volume":"82","author":"JE Brenman","year":"1995","journal-title":"Cell"},{"issue":"3","key":"ref14","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/ki.1994.98","article-title":"Effects of guanidino and uremic compounds on nitric oxide pathways","volume":"45","author":"RJ MacAllister","year":"1994","journal-title":"Kidney international"},{"issue":"Pt 14","key":"ref15","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1242\/jcs.03062","article-title":"Nitric oxide and mitochondrial biogenesis","volume":"119","author":"E Nisoli","year":"2006","journal-title":"Journal of cell science"},{"issue":"8","key":"ref16","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1042\/CS20090533","article-title":"AMPK-mediated regulation of transcription in skeletal muscle","volume":"118","author":"SL McGee","year":"2010","journal-title":"Clin Sci (Lond)"},{"issue":"9","key":"ref17","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1007\/s00726-015-2018-x","article-title":"The L-arginine\/NO pathway and homoarginine are altered in Duchenne muscular dystrophy and improved by glucocorticoids","volume":"47","author":"I Horster","year":"2015","journal-title":"Amino acids"},{"issue":"44","key":"ref18","doi-asserted-by":"crossref","first-page":"13663","DOI":"10.1073\/pnas.1512991112","article-title":"Dystrophin-glycoprotein complex regulates muscle nitric oxide production through mechanoregulation of AMPK signaling","volume":"112","author":"JF Garbincius","year":"2015","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"1","key":"ref19","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/2044-5040-2-16","article-title":"Metabolic remodeling agents show beneficial effects in the dystrophin-deficient mdx mouse model","volume":"2","author":"VE Jahnke","year":"2012","journal-title":"Skeletal muscle"},{"issue":"17","key":"ref20","doi-asserted-by":"crossref","first-page":"3478","DOI":"10.1093\/hmg\/ddr265","article-title":"Chronic AMPK activation evokes the slow, oxidative myogenic program and triggers beneficial adaptations in mdx mouse skeletal muscle","volume":"20","author":"V Ljubicic","year":"2011","journal-title":"Human molecular genetics"},{"issue":"2","key":"ref21","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.ajpath.2012.04.004","article-title":"AMPK activation stimulates autophagy and ameliorates muscular dystrophy in the mdx mouse diaphragm","volume":"181","author":"M Pauly","year":"2012","journal-title":"The American journal of pathology"},{"issue":"7","key":"ref22","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.2337\/diabetes.51.7.2074","article-title":"Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes","volume":"51","author":"N Musi","year":"2002","journal-title":"Diabetes"},{"issue":"1","key":"ref23","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/mus.24692","article-title":"Metformin increases peroxisome proliferator-activated receptor gamma Co-activator-1alpha and utrophin a expression in dystrophic skeletal muscle","volume":"52","author":"V Ljubicic","year":"2015","journal-title":"Muscle & nerve"},{"issue":"12","key":"ref24","doi-asserted-by":"crossref","first-page":"e114018","DOI":"10.1371\/journal.pone.0114018","article-title":"Metformin protects skeletal muscle from cardiotoxin induced degeneration","volume":"9","author":"F Langone","year":"2014","journal-title":"PloS one"},{"issue":"4","key":"ref25","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1212\/01.WNL.0000151976.60624.01","article-title":"L-arginine improves the symptoms of strokelike episodes in MELAS","volume":"64","author":"Y Koga","year":"2005","journal-title":"Neurology"},{"issue":"4","key":"ref26","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1111\/j.1523-1755.2002.kid555.x","article-title":"Oral L-arginine does not improve endothelial dysfunction in children with chronic renal failure","volume":"62","author":"KJ Bennett-Richards","year":"2002","journal-title":"Kidney international"},{"issue":"7","key":"ref27","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.nmd.2005.03.004","article-title":"A motor function measure for neuromuscular diseases. Construction and validation study","volume":"15","author":"C Berard","year":"2005","journal-title":"Neuromuscular disorders: NMD"},{"key":"ref28"},{"issue":"3","key":"ref29","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1212\/WNL.0b013e318225ab2e","article-title":"Functional changes in Duchenne muscular dystrophy: a 12-month longitudinal cohort study","volume":"77","author":"E Mazzone","year":"2011","journal-title":"Neurology"},{"issue":"6","key":"ref30","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.ejpn.2012.02.011","article-title":"Predicting resting energy expenditure in boys with Duchenne muscular dystrophy","volume":"16","author":"SA Elliott","year":"2012","journal-title":"European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society"},{"issue":"5","key":"ref31","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1002\/mus.21212","article-title":"Assessment of regional body composition with dual-energy X-ray absorptiometry in Duchenne muscular dystrophy: correlation of regional lean mass and quantitative strength","volume":"39","author":"AJ Skalsky","year":"2009","journal-title":"Muscle & nerve"},{"issue":"1","key":"ref32","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1148\/radiology.153.1.6089263","article-title":"Simple proton spectroscopic imaging","volume":"153","author":"WT Dixon","year":"1984","journal-title":"Radiology"},{"issue":"4","key":"ref33","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1007\/s00415-012-6733-x","article-title":"Quantitative MRI and loss of free ambulation in Duchenne muscular dystrophy","volume":"260","author":"A Fischmann","year":"2013","journal-title":"Journal of neurology"},{"issue":"1","key":"ref34","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.metabol.2012.06.011","article-title":"L-Arginine enhances glucose and lipid metabolism in rat L6 myotubes via the NO\/ c-GMP pathway","volume":"62","author":"T de Castro Barbosa","year":"2013","journal-title":"Metabolism: clinical and experimental"},{"issue":"1","key":"ref35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1074\/jbc.M110.121806","article-title":"Metformin activates AMP kinase through inhibition of AMP deaminase","volume":"286","author":"J Ouyang","year":"2011","journal-title":"The Journal of biological chemistry"},{"issue":"36","key":"ref36","doi-asserted-by":"crossref","first-page":"23925","DOI":"10.1074\/jbc.M109.021048","article-title":"Skeletal muscle AMP-activated protein kinase is essential for the metabolic response to exercise in vivo","volume":"284","author":"RS Lee-Young","year":"2009","journal-title":"The Journal of biological chemistry"},{"issue":"4","key":"ref37","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.2353\/ajpath.2006.050683","article-title":"Sarcolemmal damage in dystrophin deficiency is modulated by synergistic interactions between mechanical and oxidative\/nitrosative stresses","volume":"168","author":"RW Dudley","year":"2006","journal-title":"The American journal of pathology"},{"issue":"8","key":"ref38","doi-asserted-by":"crossref","first-page":"702","DOI":"10.18632\/aging.100358","article-title":"Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia","volume":"3","author":"DT Hall","year":"2011","journal-title":"Aging"},{"issue":"9","key":"ref39","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1007\/s00726-015-1976-3","article-title":"Differential associations of circulating asymmetric dimethylarginine and cell adhesion molecules with metformin use in patients with type 2 diabetes mellitus and stable coronary artery disease","volume":"47","author":"O Kruszelnicka","year":"2015","journal-title":"Amino acids"},{"issue":"4","key":"ref40","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1159\/000332382","article-title":"The ADMA-Metformin Hypothesis: Linking the Cardiovascular Consequences of the Metabolic Syndrome and Type 2 Diabetes","volume":"1","author":"WH Bestermann Jr","year":"2011","journal-title":"Cardiorenal medicine"},{"issue":"2","key":"ref41","doi-asserted-by":"crossref","first-page":"e89277","DOI":"10.1371\/journal.pone.0089277","article-title":"Dystropathology increases energy expenditure and protein turnover in the mdx mouse model of duchenne muscular dystrophy","volume":"9","author":"HG Radley-Crabb","year":"2014","journal-title":"PloS one"},{"issue":"4","key":"ref42","doi-asserted-by":"crossref","first-page":"7109","DOI":"10.3390\/ijms14047109","article-title":"Skeletal muscle function during exercise-fine-tuning of diverse subsystems by nitric oxide","volume":"14","author":"F Suhr","year":"2013","journal-title":"International journal of molecular sciences"},{"issue":"1","key":"ref43","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1111\/j.1469-8749.2009.03316.x","article-title":"Monitoring changes and predicting loss of ambulation in Duchenne muscular dystrophy with the Motor Function Measure","volume":"52","author":"C Vuillerot","year":"2010","journal-title":"Developmental medicine and child neurology"},{"issue":"3","key":"ref44","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1590\/S0004-282X2012000300007","article-title":"Motor function measure scale, steroid therapy and patients with Duchenne muscular dystrophy","volume":"70","author":"EC Silva","year":"2012","journal-title":"Arquivos de neuro-psiquiatria"},{"issue":"9","key":"ref45","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.nmd.2015.05.006","article-title":"Quantitative muscle MRI: A powerful surrogate outcome measure in Duchenne muscular dystrophy","volume":"25","author":"U Bonati","year":"2015","journal-title":"Neuromuscular disorders: NMD"},{"issue":"1","key":"ref46","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/path.4054","article-title":"Sildenafil reduces respiratory muscle weakness and fibrosis in the mdx mouse model of Duchenne muscular dystrophy","volume":"228","author":"JM Percival","year":"2012","journal-title":"The Journal of pathology"},{"issue":"4","key":"ref47","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/ana.24216","article-title":"Effect of sildenafil on skeletal and cardiac muscle in Becker muscular dystrophy","volume":"76","author":"N Witting","year":"2014","journal-title":"Annals of neurology"},{"issue":"1","key":"ref48","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nm.3019","article-title":"Activation of calcium signaling through Trpv1 by nNOS and peroxynitrite as a key trigger of skeletal muscle hypertrophy","volume":"19","author":"N Ito","year":"2013","journal-title":"Nature medicine"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.phrs.2013.04.009","article-title":"Ibuprofen plus isosorbide dinitrate treatment in the mdx mice ameliorates dystrophic heart structure","volume":"73","author":"C Sciorati","year":"2013","journal-title":"Pharmacological research: the official journal of the Italian Pharmacological Society"},{"issue":"4","key":"ref50","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.phrs.2012.01.006","article-title":"Nitric oxide donor and non steroidal anti inflammatory drugs as a therapy for muscular dystrophies: evidence from a safety study with pilot efficacy measures in adult dystrophic patients","volume":"65","author":"MG D'Angelo","year":"2012","journal-title":"Pharmacological research: the official journal of the Italian Pharmacological Society"},{"issue":"9","key":"ref51","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1007\/s00726-015-2012-3","article-title":"Biosynthesis of homoarginine (hArg) and asymmetric dimethylarginine (ADMA) from acutely and chronically administered free L-arginine in humans","volume":"47","author":"AA Kayacelebi","year":"2015","journal-title":"Amino acids"},{"key":"ref52"},{"key":"ref53"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0147634","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T08:35:31Z","timestamp":1600072531000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0147634"}},"subtitle":[],"editor":[{"given":"Mario D.","family":"Cordero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,1,22]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,1,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0147634","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,22]]}}}