{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:03:14Z","timestamp":1790834594862,"version":"4.1.0"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research program of China","doi-asserted-by":"publisher","award":["2014CB542402"],"award-info":[{"award-number":["2014CB542402"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81270210"],"award-info":[{"award-number":["81270210"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Microvascular Research"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1016\/j.mvr.2020.104075","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T23:14:35Z","timestamp":1600384475000},"page":"104075","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"special_numbering":"C","title":["Hypoglycemia increases endothelial-dependent vasodilation through suppressing phosphorylation at Threonine 495\/497 site of endothelial nitric oxide synthase"],"prefix":"10.1016","volume":"133","author":[{"given":"An","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deyu","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxue","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzheng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luo","family":"Suxin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.mvr.2020.104075_bb0005","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1177\/009127007701700413","article-title":"Textbook of medical physiology, 5th edition. Arthur C. Guyton","volume":"17","author":"Alexander","year":"2013","journal-title":"J. Clin. Pharmacol."},{"issue":"12","key":"10.1016\/j.mvr.2020.104075_bb0010","doi-asserted-by":"crossref","first-page":"3301","DOI":"10.2337\/dc14-0908","article-title":"Association between severe hypoglycemia, adverse macrovascular events, and inflammation in the edinburgh type 2 diabetes study","volume":"37","author":"Bedenis","year":"2014","journal-title":"Diabetes Care"},{"issue":"2\u20133","key":"10.1016\/j.mvr.2020.104075_bb0015","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/BF02815077","article-title":"Effect of starvation and insulin-induced hypoglycemia on oxidative stress scavenger system and electron transport chain complexes from rat brain, liver, and kidney","volume":"34","author":"Bhardwaj","year":"1998","journal-title":"Mol. Chem. Neuropathol."},{"issue":"55","key":"10.1016\/j.mvr.2020.104075_bb0020","first-page":"e3119","article-title":"Mesenteric artery contraction and relaxation studies using automated wire myography","author":"Bridges","year":"2011","journal-title":"Journal of Visualized Experiments Jove"},{"issue":"55","key":"10.1016\/j.mvr.2020.104075_bb0025","first-page":"e3119","author":"Bridges","year":"2011","journal-title":"Journal of Visualized Experiments Jove"},{"issue":"3","key":"10.1016\/j.mvr.2020.104075_bb0030","doi-asserted-by":"crossref","first-page":"115","DOI":"10.2337\/diaclin.24.3.115","article-title":"Hypoglycemia in type 1 and type 2 diabetes: physiology, pathophysiology, and management","volume":"24","author":"Briscoe","year":"2006","journal-title":"Clin. Diabetes"},{"issue":"12","key":"10.1016\/j.mvr.2020.104075_bb0035","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.2337\/db07-0115","article-title":"Central insulin regulates heart rate and arterial blood flow: an endothelial nitric oxide synthase-dependent mechanism altered during diabetes","volume":"56","author":"Cabou","year":"2007","journal-title":"Diabetes"},{"issue":"12","key":"10.1016\/j.mvr.2020.104075_bb0040","doi-asserted-by":"crossref","first-page":"4104","DOI":"10.2337\/dc13-0750","article-title":"Vitamin C further improves the protective effect of glucagon-like peptide-1 on acute hypoglycemia-induced oxidative stress, inflammation, and endothelial dysfunction in type 1 diabetes","volume":"36","author":"Ceriello","year":"2013","journal-title":"Diabetes Care"},{"issue":"7327","key":"10.1016\/j.mvr.2020.104075_bb0045","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1038\/nature09599","article-title":"S-glutathionylation uncouples enos and regulates its cellular and vascular function","volume":"468","author":"Chen","year":"2010","journal-title":"Nature"},{"issue":"7","key":"10.1016\/j.mvr.2020.104075_bb0050","article-title":"Pkc-dependent phosphorylation of Enos at T495 regulates Enos coupling and endothelial barrier function in response to G+-toxins","volume":"9","author":"Chen","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.mvr.2020.104075_bb0055","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0014-2999(97)00181-7","article-title":"Role of nitric oxide in the effects of hypoglycemia on the cerebral circulation in awake goats","volume":"330","author":"Dieguez","year":"1997","journal-title":"Eur. J. Pharmacol."},{"issue":"8\u20139","key":"10.1016\/j.mvr.2020.104075_bb0060","first-page":"252","article-title":"Nitric oxide modulation of metabolic and haemodynamic balance","volume":"106","author":"Dzurik","year":"2005","journal-title":"Bratisl. Lek. Listy"},{"issue":"8","key":"10.1016\/j.mvr.2020.104075_bb0065","article-title":"Blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in patients with symptoms suggesting reactive hypoglycemia","volume":"49","author":"Filho","year":"2016","journal-title":"Braz. J. Med. Biol. Res"},{"issue":"2","key":"10.1016\/j.mvr.2020.104075_bb0070","doi-asserted-by":"crossref","first-page":"519","DOI":"10.2337\/db09-0421","article-title":"Ventromedial hypothalamic nitric oxide production is necessary for hypoglycemia detection and counterregulation","volume":"59","author":"Fioramonti","year":"2010","journal-title":"Diabetes"},{"key":"10.1016\/j.mvr.2020.104075_bb0075","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1152\/ajpregu.00323.2002","article-title":"Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase","volume":"284","author":"Fleming","year":"2003","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"issue":"7","key":"10.1016\/j.mvr.2020.104075_bb0080","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1093\/eurheartj\/ehr304","article-title":"Nitric oxide synthases: regulation and function","volume":"33","author":"F\u00f6rstermann","year":"2012","journal-title":"Eur. Heart J"},{"issue":"1","key":"10.1016\/j.mvr.2020.104075_bb0085","doi-asserted-by":"crossref","first-page":"155","DOI":"10.2337\/dc16-2215","article-title":"Glucose concentrations of less than 3.0 mmol\/l (54 mg\/dl) should be reported in clinical trials: a joint position statement of the American Diabetes Association and the European Association for the Study of Diabetes","volume":"40","author":"Group, International Hypoglycaemia Study","year":"2017","journal-title":"Diabetes Care"},{"key":"10.1016\/j.mvr.2020.104075_bb0090","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/j.jacc.2005.11.046","article-title":"Metabolic syndrome: connecting and reconciling cardiovascular and diabetes worlds","volume":"47","author":"Grundy","year":"2006","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.mvr.2020.104075_bb0095","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1097\/01.fjc.0000211729.30927.4d","article-title":"Metabolic syndrome, new onset diabetes, and new end points in cardiovascular trials","volume":"47","author":"Haffner","year":"2006","journal-title":"J Cardiovasc Pharmacol"},{"issue":"6","key":"10.1016\/j.mvr.2020.104075_bb0100","doi-asserted-by":"crossref","first-page":"H3768","DOI":"10.1152\/ajpheart.00486.2007","article-title":"Inducible and myocyte-specific inhibition of Pkc\u03b1 enhances cardiac contractility and protects against infarction-induced heart failure","volume":"293","author":"Hambleton","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"issue":"6","key":"10.1016\/j.mvr.2020.104075_bb0105","doi-asserted-by":"crossref","first-page":"H3768","DOI":"10.1152\/ajpheart.00486.2007","article-title":"Inducible and myocyte-specific inhibition of Pkc\u03b1 enhances cardiac contractility and protects against infarction-induced heart failure","volume":"293","author":"Hambleton","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"issue":"4","key":"10.1016\/j.mvr.2020.104075_bb0110","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nrm3311","article-title":"Ampk: a nutrient and energy sensor that maintains energy homeostasis","volume":"13","author":"Hardie","year":"2012","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"issue":"002","key":"10.1016\/j.mvr.2020.104075_bb0115","first-page":"14","article-title":"Detection of blood biochemical indexes in cows","volume":"041","author":"He","year":"2005","journal-title":"Chin. J. Vet. Med."},{"issue":"37","key":"10.1016\/j.mvr.2020.104075_bb0120","doi-asserted-by":"crossref","first-page":"25256","DOI":"10.1074\/jbc.M802455200","article-title":"Bidirectional actions of hydrogen peroxide on endothelial nitric-oxide synthase phosphorylation and function: co-commitment and interplay of Akt and Ampk*","volume":"283","author":"Hu","year":"2008","journal-title":"J. Biol. Chem."},{"issue":"6","key":"10.1016\/j.mvr.2020.104075_bb0125","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s001250051675","article-title":"Protein kinase C activation: isozyme-specific effects on metabolism and cardiovascular complications in diabetes","volume":"44","author":"Idris","year":"2001","journal-title":"Diabetologia"},{"issue":"6","key":"10.1016\/j.mvr.2020.104075_bb0130","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1111\/jdi.12678","article-title":"Low glucose induces mitochondrial reactive oxygen species via fatty acid oxidation in bovine aortic endothelial cells","volume":"8","author":"Kajihara","year":"2017","journal-title":"J. Diabetes Investig."},{"issue":"12","key":"10.1016\/j.mvr.2020.104075_bb0135","doi-asserted-by":"crossref","first-page":"749","DOI":"10.3858\/emm.2012.44.12.083","article-title":"Cinnamyl alcohol attenuates vasoconstriction by activation of K+ channels via no-Cgmp-protein kinase G pathway and inhibition of rho-kinase","volume":"44","author":"Kang","year":"2012","journal-title":"Exp. Mol. Med."},{"issue":"6","key":"10.1016\/j.mvr.2020.104075_bb0140","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0066176","article-title":"Hypo- and hyperglycemia impair endothelial cell actin alignment and nitric oxide synthase activation in response to shear stress","volume":"8","author":"Kemeny","year":"2013","journal-title":"Plos One"},{"issue":"6","key":"10.1016\/j.mvr.2020.104075_bb0145","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0011098","article-title":"Cyclic nucleotide-gated channels contribute to thromboxane a 2-induced contraction of rat small mesenteric arteries","volume":"5","author":"Leung","year":"2010","journal-title":"Plos One"},{"issue":"1","key":"10.1016\/j.mvr.2020.104075_bb0150","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.bbrc.2012.04.119","article-title":"Potential role of 20s proteasome in maintaining stem cell integrity of human bone marrow stromal cells in prolonged culture expansion","volume":"422","author":"Lu","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"02","key":"10.1016\/j.mvr.2020.104075_bb0155","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1160\/TH14-04-0360","article-title":"Antithrombin up-regulates amp-activated protein kinase signalling during myocardial ischaemia\/reperfusion injury","volume":"113","author":"Ma","year":"2015","journal-title":"Thromb. Haemost."},{"key":"10.1016\/j.mvr.2020.104075_bb0160","doi-asserted-by":"crossref","first-page":"6123","DOI":"10.1074\/jbc.275.9.6123","article-title":"Enhanced electron flux and reduced calmodulin dissociation may explain \u2018calcium-independent\u2019 eNOS activation by phosphorylation","volume":"275","author":"McCabe","year":"2000","journal-title":"J. Biol. Chem."},{"issue":"6","key":"10.1016\/j.mvr.2020.104075_bb0165","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.2337\/dc09-9029","article-title":"American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control","volume":"32","author":"Moghissi","year":"2009","journal-title":"Diabetes Care"},{"issue":"5","key":"10.1016\/j.mvr.2020.104075_bb0170","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.bbi.2009.11.013","article-title":"Moderate recurrent hypoglycemia during early development leads to persistent changes in affective behavior in the rat","volume":"24","author":"Moore","year":"2010","journal-title":"Brain, Behav., Immun."},{"issue":"2","key":"10.1016\/j.mvr.2020.104075_bb0175","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s12028-009-9311-z","article-title":"Moderate hypoglycemia is associated with vasospasm, cerebral infarction, and 3-month disability after subarachnoid hemorrhage","volume":"12","author":"Naidech","year":"2010","journal-title":"Neurocrit. Care"},{"issue":"8","key":"10.1016\/j.mvr.2020.104075_bb0180","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1111\/j.1582-4934.2010.01174.x","article-title":"Pkc\u03b2ii inhibition attenuates myocardial infarction induced heart failure and is associated with a reduction of fibrosis and pro-inflammatory responses","volume":"15","author":"Palaniyandi","year":"2011","journal-title":"J. Cell. Mol. Med."},{"issue":"5","key":"10.1016\/j.mvr.2020.104075_bb0185","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1161\/01.RES.0000179775.04114.45","article-title":"Pkcalpha activates Enos and increases arterial blood flow in vivo","volume":"97","author":"Partovian","year":"2005","journal-title":"Circ. Res."},{"issue":"8","key":"10.1016\/j.mvr.2020.104075_bb0190","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.tem.2015.05.010","article-title":"Ampk: energy sensor and survival mechanism in the ischemic heart","volume":"26","author":"Qi","year":"2015","journal-title":"Trends Endocrinol. Metab."},{"key":"10.1016\/j.mvr.2020.104075_bb0195","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1089\/152091504774198133","article-title":"The role of glucosensing neurons in the detection of hypoglycemia","volume":"6","author":"Routh","year":"2004","journal-title":"Diabetes Technol. Ther."},{"issue":"9","key":"10.1016\/j.mvr.2020.104075_bb0200","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.4158\/EP161199.RA","article-title":"The diabetes epidemic in China: an integrated review of national surveys running title: The Diabetes Epidemic in China","volume":"22","author":"Shen","year":"2016","journal-title":"Endocr Pract"},{"issue":"23","key":"10.1016\/j.mvr.2020.104075_bb0205","doi-asserted-by":"crossref","first-page":"4561","DOI":"10.1007\/s00018-015-2021-0","article-title":"Endothelial nitric oxide synthase in the microcirculation","volume":"72","author":"Shu","year":"2015","journal-title":"Cellular & Molecular Life Sciences Cmls"},{"issue":"23","key":"10.1016\/j.mvr.2020.104075_bb0210","doi-asserted-by":"crossref","first-page":"4561","DOI":"10.1007\/s00018-015-2021-0","article-title":"Endothelial nitric oxide synthase in the microcirculation","volume":"72","author":"Shu","year":"2015","journal-title":"Cellular & Molecular Life Sciences Cmls"},{"issue":"3","key":"10.1016\/j.mvr.2020.104075_bb0215","first-page":"44","article-title":"Hypoglycemia: physiology, signs, and symptoms","volume":"13","author":"Taylor","year":"1983","journal-title":"Nursing"},{"issue":"3","key":"10.1016\/j.mvr.2020.104075_bb0220","first-page":"712","article-title":"Acute exposure to low glucose rapidly induces endothelial dysfunction and mitochondrial oxidative stress: role for amp kinase","volume":"32","author":"Wang","year":"2012","journal-title":"ArteriosclerThrombVascBiol"},{"issue":"7","key":"10.1016\/j.mvr.2020.104075_bb0225","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.2337\/dc10-0013","article-title":"Effects of acute insulin-induced hypoglycemia on indices of inflammation: putative mechanism for aggravating vascular disease in diabetes","volume":"33","author":"Wright","year":"2010","journal-title":"Diabetes Care"},{"issue":"10","key":"10.1016\/j.mvr.2020.104075_bb0230","doi-asserted-by":"crossref","first-page":"6366","DOI":"10.1074\/jbc.M511178200","article-title":"Activation of protein kinase C\u03b6 by peroxynitrite regulates Lkb1-dependent Amp-activated protein kinase in cultured endothelial cells","volume":"281","author":"Xie","year":"2006","journal-title":"J. Biol. Chem"},{"issue":"7","key":"10.1016\/j.mvr.2020.104075_bb0235","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1161\/CIRCULATIONAHA.107.744490","article-title":"Phosphorylation of Lkb1 at serine 428 by protein kinase C-\u0396 is required for metformin-enhanced activation of the amp-activated protein kinase in endothelial cells","volume":"117","author":"Xie","year":"2008","journal-title":"Circulation"},{"key":"10.1016\/j.mvr.2020.104075_bb0240","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ab.2017.08.017","article-title":"Measurement of o-glcnacylated endothelial nitric oxide synthase by using 2\u2032,5\u2032-adp-sepharose pull-down assay","volume":"537","author":"Yang","year":"2017","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.mvr.2020.104075_bb0245","doi-asserted-by":"crossref","first-page":"4149","DOI":"10.12659\/MSM.916517","article-title":"Role of phosphorylated AMP-activated protein kinase (AMPK) in myocardial insulin resistance after myocardial ischemia-reperfusion during cardiopulmonary bypass surgery in dogs","volume":"25","author":"Zhang","year":"2019","journal-title":"Med. Sci. Monit."}],"container-title":["Microvascular Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026286220301357?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026286220301357?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T05:57:27Z","timestamp":1758434247000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0026286220301357"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":49,"alternative-id":["S0026286220301357"],"URL":"https:\/\/doi.org\/10.1016\/j.mvr.2020.104075","relation":{},"ISSN":["0026-2862"],"issn-type":[{"value":"0026-2862","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hypoglycemia increases endothelial-dependent vasodilation through suppressing phosphorylation at Threonine 495\/497 site of endothelial nitric oxide synthase","name":"articletitle","label":"Article Title"},{"value":"Microvascular Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.mvr.2020.104075","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"104075"}}