{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363670319940325632.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.2337/diabetes.53.2.336"}},{"identifier":{"@type":"URI","@value":"https://journals.org/diabetes/diabetes/article-pdf/53/2/336/375393/336.pdf"}},{"identifier":{"@type":"URI","@value":"https://diabetesjournals.org/diabetes/article-pdf/53/2/336/375393/336.pdf"}},{"identifier":{"@type":"NAID","@value":"30026270738"}}],"dc:title":[{"@value":"Prevention of Obesity and Insulin Resistance in Mice Lacking Plasminogen Activator Inhibitor 1"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Increased plasminogen activator inhibitor 1 (PAI-1) has been linked to not only thrombosis and fibrosis but also to obesity and insulin resistance. Increased PAI-1 levels have been presumed to be consequent to obesity. We investigated the interrelationships of PAI-1, obesity, and insulin resistance in a high-fat/high-carbohydrate (HF) diet–induced obesity model in wild-type (WT) and PAI-1–deficient mice (PAI-1−/−). Obesity and insulin resistance developing in WT mice on an HF diet were completely prevented in mice lacking PAI-1. PAI-1−/− mice on an HF diet had increased resting metabolic rates and total energy expenditure compared with WT mice, along with a marked increase in uncoupling protein 3 mRNA expression in skeletal muscle, likely mechanisms contributing to the prevention of obesity. In addition, insulin sensitivity was enhanced significantly in PAI-1−/− mice on an HF diet, as shown by euglycemic-hyperinsulinemic clamp studies. Peroxisome proliferator–activated receptor (PPAR)-γ and adiponectin mRNA, key control molecules in lipid metabolism and insulin sensitivity, were maintained in response to an HF diet in white adipose tissue in PAI-1−/− mice, contrasting with downregulation in WT mice. This maintenance of PPAR-γ and adiponectin may also contribute to the observed maintenance of body weight and insulin sensitivity in PAI-1−/− mice. Treatment in WT mice on an HF diet with the angiotensin type 1 receptor antagonist to downregulate PAI-1 indeed inhibited PAI-1 increases and ameliorated diet-induced obesity, hyperglycemia, and hyperinsulinemia. PAI-1 deficiency also enhanced basal and insulin-stimulated glucose uptake in adipose cells in vitro. Our data suggest that PAI-1 may not merely increase in response to obesity and insulin resistance, but may have a direct causal role in obesity and insulin resistance. Inhibition of PAI-1 might provide a novel anti-obesity and anti–insulin resistance treatment.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1383670319940325641","@type":"Researcher","foaf:name":[{"@value":"Li-Jun Ma"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319940325636","@type":"Researcher","foaf:name":[{"@value":"Su-Li Mao"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319940325635","@type":"Researcher","foaf:name":[{"@value":"Kevin L. Taylor"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319940325639","@type":"Researcher","foaf:name":[{"@value":"Talerngsak Kanjanabuch"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319940325640","@type":"Researcher","foaf:name":[{"@value":"YouFei Guan"}],"jpcoar:affiliationName":[{"@value":"Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319940325632","@type":"Researcher","foaf:name":[{"@value":"YaHua Zhang"}],"jpcoar:affiliationName":[{"@value":"Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319940325634","@type":"Researcher","foaf:name":[{"@value":"Nancy J. Brown"}],"jpcoar:affiliationName":[{"@value":"Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319940325504","@type":"Researcher","foaf:name":[{"@value":"Larry L. Swift"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319940325633","@type":"Researcher","foaf:name":[{"@value":"Owen P. McGuinness"}],"jpcoar:affiliationName":[{"@value":"Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319940325638","@type":"Researcher","foaf:name":[{"@value":"David H. Wasserman"}],"jpcoar:affiliationName":[{"@value":"Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319940325637","@type":"Researcher","foaf:name":[{"@value":"Douglas E. Vaughan"}],"jpcoar:affiliationName":[{"@value":"Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319940325642","@type":"Researcher","foaf:name":[{"@value":"Agnes B. Fogo"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00121797"},{"@type":"EISSN","@value":"1939327X"}],"prism:publicationName":[{"@value":"Diabetes"}],"dc:publisher":[{"@value":"American Diabetes Association"}],"prism:publicationDate":"2004-02-01","prism:volume":"53","prism:number":"2","prism:startingPage":"336","prism:endingPage":"346"},"reviewed":"false","url":[{"@id":"https://journals.org/diabetes/diabetes/article-pdf/53/2/336/375393/336.pdf"},{"@id":"https://diabetesjournals.org/diabetes/article-pdf/53/2/336/375393/336.pdf"}],"createdAt":"2007-03-06","modifiedAt":"2022-11-02","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050567903510963456","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Effects of Propolis Extract and Propolis-Derived Compounds on Obesity and Diabetes : Knowledge from Cellular and Animal Models"}]},{"@id":"https://cir.nii.ac.jp/crid/1050850490559689472","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Inhibition of Plasminogen Activator Inhibitor-1 Activation Suppresses High Fat Diet-Induced Weight Gain via Alleviation of Hypothalamic Leptin Resistance."}]},{"@id":"https://cir.nii.ac.jp/crid/1360004230200511744","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The allenic carotenoid fucoxanthin, a novel marine nutraceutical from brown seaweeds"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285706118886272","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Role of mesenchymal stem cell-derived fibrinolytic factor in tissue regeneration and cancer progression"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285706255654528","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Role of plasminogen activator inhibitor-1 in glucocorticoid-induced muscle change in mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285707506088320","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Effect of dibutyryl cyclic adenosine monophosphate on the gene expression of plasminogen activator inhibitor-1 and tissue factor in adipocytes"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285712520615424","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Plasminogen Activator Inhibitor-1 Is Involved in Impaired Bone Repair Associated with Diabetes in Female Mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285713896083584","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Plasminogen Activator Inhibitor-1 Is Involved in Streptozotocin-Induced Bone Loss in Female Mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285713896215552","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Role of Plasminogen Activator Inhibitor-1 in Glucocorticoid-Induced Diabetes and Osteopenia in Mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360302864783625472","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Heterogeneity in the effect of marked weight loss on metabolic function in women with obesity"}]},{"@id":"https://cir.nii.ac.jp/crid/1360306904409091584","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Inter-Organ Communication Involved in Brown Adipose Tissue Thermogenesis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360565168139028608","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"<scp>PAI</scp>‐1, progress in understanding the clinical problem and its aetiology"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848655007575296","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Adipose Tissue‐Derived Plasminogen Activator Inhibitor‐1 Function and Regulation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848661868381312","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Plasminogen Activator Inhibitor-1 Deficiency Ameliorates Insulin Resistance and Hyperlipidemia But Not Bone Loss in Obese Female Mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204443504256","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"メタボリックシンドロームと凝固・線溶―ＰＡＩ‐１に焦点をあてて―"},{"@language":"en","@value":"The coagulation and fibrinolysis activity in metabolic syndrome"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204443578496","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"PAI-1 and lifestyle-related illnesses"},{"@language":"ja","@value":"ＰＡＩ－１と生活習慣病"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204444175360","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Anti-thrombotic therapy for metabolic syndrome"},{"@language":"ja","@value":"メタボリックシンドロームの血栓傾向と抗血栓療法"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001206326417408","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Caffeine-Stimulated Intestinal Epithelial Cells Suppress Lipid Accumulation in Adipocytes"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679148748928","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Structure-Activity Relationships of New 2-Acylamino-3-thiophenecarboxylic Acid Dimers as Plasminogen Activator Inhibitor-1 Inhibitors"},{"@value":"ChemInform Abstract: Structure—Activity Relationships of New 2‐Acylamino‐3‐thiophenecarboxylic Acid Dimers as Plasminogen Activator Inhibitor‐1 Inhibitors."}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679422042624","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"A pathological role of PAI-1 in metabolic syndrome"},{"@value":"生活習慣病とPAI-1"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679427651328","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"骨代謝異常におけるPlasminogen Activator Inhibitor-1 の役割"},{"@language":"en","@value":"Role of plasmionogen activator inhibitor-1 in the pathogenesis of bone metabolism abnormalities"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679646875776","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"脂肪細胞から分泌される生理活性物質アディポカイン遺伝子発現制御"},{"@language":"en","@value":"Adipocyte-derived factors, adipokines gene regulation."},{"@language":"ja-Kana","@value":"シボウ サイボウ カラ ブンピツ サレル セイリ カッセイ ブッシツ アディポカイン イデンシ ハツゲン セイギョ"}]},{"@id":"https://cir.nii.ac.jp/crid/1520290884525520768","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@value":"第26回[日本臨床検査医学会]東海・北陸支部例会 シンポジウム 血栓傾向の病態機序と臨床検査(1)メタボリックシンドロームにおける血栓傾向と臨床検査"},{"@language":"ja-Kana","@value":"ダイ 26カイ ニホン リンショウ ケンサ イガクカイ トウカイ ホクリク シブ レイカイ シンポジウム ケッセン ケイコウ ノ ビョウタイ キジョ ト リンショウ ケンサ 1 メタボリック シンドローム ニ オケル ケッセン ケイコウ ト リンショウ ケンサ"}]},{"@id":"https://cir.nii.ac.jp/crid/1571698600694264448","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"アディポサイトカインを標的とした大腸がん予防方法"},{"@language":"en","@value":"SEARCHING FOR EFFECTIVE COLON CANCER PREVENTION METHODS TARGETING ADIPOCYTOKINES"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.2337/diabetes.53.2.336"},{"@type":"CIA","@value":"30026270738"},{"@type":"CROSSREF","@value":"10.1002/jsfa.4353_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.2491/jjsth.19.55_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.3389/fphar.2020.00943_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.1007/s00018-015-2035-7_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.1007/s00774-017-0825-8_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.1371/journal.pone.0092686_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.2337/db14-1192_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.2491/jjsth.18.269_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.1172/jci.insight.169541_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.1007/978-981-97-4584-5_11_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.1111/j.1365-2141.2012.09074.x_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.3330/hikakuseiriseika.26.47_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.2491/jjsth.17.120_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.1002/cphy.c160004_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.1210/en.2013-1888_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.3390/molecules24234394_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.1248/cpb.58.615_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.2491/jjsth.18.607_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.1016/j.thromres.2011.03.005_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.2491/jjsth.26.619_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.3177/jnsv.63.331_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"},{"@type":"CROSSREF","@value":"10.2337/db12-1552_references_DOI_Q9CxrrkIpIZQ9GSfsWFTfNszT9M"}]}