{"created":"2023-07-27T06:28:34.641721+00:00","id":13171,"links":{},"metadata":{"_buckets":{"deposit":"4e6b68df-0dbb-4b64-8766-d9866c2d0e3d"},"_deposit":{"created_by":3,"id":"13171","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"13171"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00013171","sets":["1132:1133:1134"]},"author_link":["21036","413","21035","21037","21038","62","225"],"item_4_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2006-11-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"11","bibliographicPageEnd":"1472","bibliographicPageStart":"1464","bibliographicVolumeNumber":"55","bibliographic_titles":[{"bibliographic_title":"Metabolism: Clinical and Experimental"}]}]},"item_4_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Plasminogen activator inhibitor 1 (PAI-1) is an important mediator of atherosclerosis and liver fibrosis in insulin resistance. Circulating levels of PAI-1 are elevated in obese individuals, and PAI-1 messenger RNA is significantly higher in the livers of obese type 2 diabetic individuals than in nonobese type 2 diabetic individuals. To address the mechanism underlying the up-regulation of hepatic PAI-1 in obesity, we tested the effects of tumor necrosis factor α (TNF-α), an important link between obesity and insulin resistance, on PAI-1 production in the nonmalignant human hepatocyte cell line, THLE-5b. Incubation of THLE-5b cells with TNF-α stimulated PAI-1 production via protein kinase C-, mitogen-activated protein kinase-, protein tyrosine kinase-, and nuclear factor-κB-dependent pathways. A thiazolidinedione, pioglitazone, reduced TNF-α-induced PAI-1 production by 32%, via protein kinase C- and nuclear factor-κB-dependent pathways. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor cerivastatin inhibited TNF-α-induced PAI-1 production by 59%, which was reversed by coincubation with mevalonic acid. In conclusion, obesity and TNF-α up-regulation of PAI-1 expression in human hepatocytes may contribute to the impairment of the fibrinolytic system, leading to the development of atherosclerosis and liver fibrosis in insulin-resistant individuals. A thiazolidinedione and a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor may thus be candidate drugs to inhibit obesity-associated hepatic PAI-1 production. © 2006","subitem_description_type":"Abstract"}]},"item_4_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学大学院医学系研究科環境社会医学","subitem_description_type":"Other"}]},"item_4_publisher_17":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Elsevier BV"}]},"item_4_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1016/j.metabol.2006.06.016","subitem_relation_type_select":"DOI"}}]},"item_4_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"http://www.elsevier.com/locate/issn/00260495","subitem_relation_type_select":"URI"}}]},"item_4_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0026-0495","subitem_source_identifier_type":"ISSN"}]},"item_4_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Takeshita, 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